Systems and methods for neurological traffic and/or receptor functional evaluation and/or modification

ABSTRACT

Systems and methods for controlled sympathectomy procedures for neuromodulation are disclosed. A system for controlled micro ablation procedures is disclosed. A guidewire including one or more sensors or electrodes for accessing and recording physiologic information from one or more anatomical sites within the parenchyma of an organ as part of a physiologic monitoring session, a diagnostic test, or a neuromodulation procedure is disclosed. A guidewire including one or more sensors and/or a means for energy delivery, for performing a neuromodulation procedure within a small vessel within a body is disclosed.

CROSS-REFERENCES TO RELATED APPLICATION

The present application is a continuation of U.S. patent applicationSer. No. 14/780,068, filed Sep. 25, 2015, which is a national stage ofInternational Application PCT/US2014/031962 which claims benefit of andpriority to U.S. Provisional Application Ser. No. 61/805,523 filed onMar. 27, 2013, entitled “Systems and Methods for Neurological trafficand/or Receptor Functional Evaluation and/or Modification”, by LandyToth et al., and U.S. Provisional Application Ser. No. 61/885,540 filedon Oct. 2, 2013, entitled “Systems and Methods for Neurological trafficand/or Receptor Functional Evaluation and/or Modification”, by LandyToth et al. the entire contents of which are incorporated by referenceherein for all purposes.

BACKGROUND Technical Field

The present disclosure relates to the field of surgical modification ofneurological function as well as methods for locating, monitoring and/ormapping electrophysiological signals before, during and/or following astimulus and/or surgical procedure, such as denervation orneuromodulation.

Background

Congestive heart failure, hypertension, diabetes, sleep apnea, andchronic renal failure have many different initial causes; however, allmay include some form of sympathetic hyperactivity. Chemoreceptors,baroreceptors, stretch-receptors, and sympathetic nerves communicatesignals with sympathetic centers located in the spinal cord and brainvia afferent nerve activity, increasing systemic sympathetic tone;meanwhile, through efferent activity, nerves and arteries participate insympathetic hyperactivity in response to signals from the brain, furtherincreasing systemic sympathetic tone.

Sympathetic activation can initially be beneficial but eventuallybecomes maladaptive. In a state of sympathetic hyperactivity, a numberof pathological events take place: abnormalities of hormonal secretionsuch as increased catecholamine, renine and angiotensin II levels,increased blood pressure due to peripheral vascular constriction and/orwater and sodium retention, renal failure due to impaired glomerularfiltration and nephron loss, cardiac dysfunction and heart failure dueto left ventricular hypertrophy and myocyte loss, stroke, and evendiabetes. Therefore, modulation (reduction/removal) of this increasedsympathetic activity can slow or prevent the progression of thesediseases.

Although ablation of such nerves can have positive effects on drugresistant hypertension and glucose metabolism abnormality, currentmethodologies for denervation (e.g. ablation via a range of energysources or chemistries) are conducted without adequate feedback (withrespect to the site of a denervation event, the extent of denervation,the effect of denervation on local physiology, etc.) and cases ofnon-responders in the clinic to treatment remains a concern.

SUMMARY

One objective of this disclosure is to provide a microsurgical tool formonitoring, evaluating the function of, mapping, and/or modulatingelectrophysiological activity in the vicinity of a lumen within a body.Another objective is to provide systems and methods for evaluating theextent of a neuromodulation procedure such as a neuromodulating surgeryor stimulation. Another objective is to provide a sensing and/orablating guidewire for monitoring physiologic signals, and/or performinga neuromodulation procedure in a body, particularly within or in thevicinity of the parenchyma of an organ, such as a kidney, a carotidbody, a prostate, a pancreas, a liver, a stomach, an intestine, aspleen, one or more ganglia, etc. and/or the perivascular neural supplyto the organ. Another objective is to provide a system and method forevaluating the sympathetic tone of a subject. Yet another objective isto provide systems and/or devices for neuromodulating an anatomical sitein the vicinity of a lumen within a body. Another objective is toprovide systems and/or devices for adjusting the functionality of anorgan process, a receptor process, a cellular process or the like in thevicinity of a lumen within a body.

The above objectives are wholly or partially met by devices, systems,and methods according to the appended claims in accordance with thepresent disclosure. Features and aspects are set forth in the appendedclaims, in the following description, and in the annexed drawings inaccordance with the present disclosure.

According to a first aspect there is provided, a microsurgical tool formonitoring electrophysiological activity within the vicinity of a lumen,the microsurgical tool including a microfinger in accordance with thepresent disclosure having a substantially elongate structure configuredso as to bias a region thereof against a wall of the lumen upondeployment within the lumen, and a sensing tip in accordance with thepresent disclosure electrically and mechanically coupled to themicrofinger in the vicinity of the region, configured to interface withthe wall of the lumen, the sensing tip configured to convey one or moreelectrophysiological signals associated with the activity.

In aspects, one or more of the electrophysiological signals may berelated to one or more of water concentration, tone, evoked potential,remote stimulation of nervous activity, an electromyographic signal[EMG], a mechanomyographic signal [MMG], a local field potential, anelectroacoustic event, vasodilation, vessel wall stiffness, musclesympathetic nerve activity (MSNA), central sympathetic drive (e.g.bursts per minute, bursts per heartbeat, etc.), tissue tone, nervetraffic (e.g. post ganglionic nerve traffic in the peroneal nerve,celiac ganglion, superior mesenteric ganglion, aorticorenal ganglion,renal ganglion, and/or related nervous system structures), combinationsthereof, or the like.

In aspects, one or more of the sensing tips may include one or moreelectrodes, a needle electrode, a force sensor, mechanomyographic (MMG)sensing element, a strain sensor, a compliance sensor, a temperaturesensor, combinations thereof, or the like each in accordance with thepresent disclosure. In aspects, one or more sensing tips may beelectrically coupled with a microcircuit, the microcircuit configured tocondition the signal.

In aspects, a system/surgical tool in accordance with the presentdisclosure may be used to access, monitor, and/or to treat one or moresensory receptors: Ampullae of Lorenzini (respond to electric field,salinity, temperature, etc.), baroreceptors, chemoreceptors,hydroreceptors, mechanoreceptors, nociceptors, osmoreceptors (osmolaritysensing), photoreceptors, proprioceptors, thermoreceptors, combinationsthereof, and the like.

According to aspects there is provided, an elongate medical deviceincluding one or more sensing tips each in accordance with the presentdisclosure. The elongate medical device may be configured for placementwithin a vessel, for delivery to or within the parenchyma of an organinto which the vessel extends.

In aspects, the elongate medical device may be a guidewire configuredfor nerve monitoring, electrophysiological monitoring, stimulation,and/or ablation procedures.

In aspects, a guidewire in accordance with the present disclosure may beconfigured to provide a path over which a second surgical tool may bedelivered to the vessel, the guidewire sensing tip configured to monitorone or more physiologic functions relevant to the operation and/orevaluation of a procedure performed by the surgical tool.

In aspects, a guidewire and/or sensing tip in accordance with thepresent disclosure may be dimensioned and configured for placement intothe parenchyma of an organ, a renal cortex of a kidney, an adrenalgland, a vessel connected with the adrenal gland, an adrenal medulla,and/or a renal pelvis of a kidney.

In aspects, a guidewire in accordance with the present disclosure mayinclude a plurality of zones arranged along the length thereof, eachzone configured for sensing local electrophysiological activity,stimulating local neural anatomy, and/or neuromodulating local neuralanatomy (e.g. ablating, denervating, etc.). In aspects, a guidewire inaccordance with the present disclosure may include a sensing zonelocated at the distal tip thereof, an ablating/stimulating zone locatedalong the length of the guidewire proximally to the distal tip, and asecond sensing zone located along the length of the guidewire proximallyto the ablating/stimulating zone. In aspects, functions performed withineach zone during a procedure may be coordinated by a controller inaccordance with the present disclosure for purposes of diagnosis,determining the extent of a procedure, performing a neuromodulationprocedure, denervating a neural structure, combinations thereof, or thelike.

In aspects, a guidewire in accordance with the present disclosure may besized with a diameter of less than 1 mm, less than 0.75 mm, less than0.5 mm, less than 0.25 mm, etc. In aspects, the guidewire may beconfigured with a shape set region, configured to bias one or moreregions of the guidewire against a wall of a lumen into which it hasbeen placed. In aspects, the guidewire may include a wire basket, ahelical region, a balloon, etc. in order to provide such bias against anadjacent lumen wall. In aspects, the shape set region may be retractablycollapsible into a delivery sheath (i.e. a sheath provided over theguidewire sized and dimensioned for delivery thereof to an anatomicalsite of interest). In aspects, the shape set region may be deployed soas to bias against a wall of a lumen into which it is placed by anactuation procedure, retraction of a delivery sheath, protrusion of theguidewire distal tip beyond the distal tip of a delivery sheath, etc.

In aspects, a guidewire in accordance with the present disclosure mayinclude a bulbous feature located within the vicinity of the distal tipthereof, the bulbous feature configured to bottom out the guidewirewithin a lumen (e.g. when the lumen diameter approaches that of thebulbous feature, between a step between a feeding lumen and a treatmentlumen, etc.). Such a feature may be advantageous to position the distaltip of the guidewire within a treatment lumen (e.g. a vessel, an artery,a vein, a tubule, etc.), to provide hemostasis to the treatment lumen,etc.

In aspects, a guidewire in accordance with the present disclosure mayinclude a microelectronic circuit embedded within or coupled to thedistal tip thereof, as well as coupled to an interconnect and/orcontroller coupled to the proximal end thereof, configured to controlsignal flow to/from one or more zones of the guidewire for purposes ofperforming a procedure in accordance with the present disclosure.

According to aspects there is provided, a method for treating ananatomical site within a body, including imaging the anatomical site(e.g. with a computed tomography system, high-resolution computedtomography (HRCT), magnetic resonance imaging (MRI), functional magneticresonance imaging (fMRI), positron emission tomography, ultrasound,optical coherence tomography (OCT), combinations thereof, or the like)to produce one or more images (e.g. 2D images, 3D images, etc.) thereof,guiding a guidewire, device, and/or aspects of a system in accordancewith the present disclosure to within the vicinity of the anatomicalsite (optionally in combination with the images), and performing aprocedure, and/or treating the anatomical site (e.g. via ablation,chemical delivery, energy delivery, etc.). In aspects, the procedure mayinclude sensing one or more physiologic aspects of the anatomical siteand/or a bodily process related thereto, stimulating the anatomicalsite, etc.

In aspects, a method in accordance with the present disclosure mayinclude advancing a guidewire in accordance with the present disclosureuntil it “bottoms out” against the walls of the lumen including and/orcoupled to the anatomical site.

In aspects, a method in accordance with the present disclosure mayinclude releasing a chemical substance in accordance with the presentdisclosure into, through the wall of, and/or into the adventitia arounda lumen coupled with the anatomical site, and/or associated organ.

In aspects, a method in accordance with the present disclosure mayinclude monitoring one or more physiologic processes with the distal tipof a guidewire in accordance with the present disclosure, before,during, and/or after the release of the chemical substance. The methodmay include assessing the efficacy of a procedure (e.g. ablation,chemical release, chemical ablation, RF ablation, ultrasound ablation,hypothermic ablation, radiosurgical ablation, etc.). In aspects, themethod may include inducing a temporary neural block, monitoring theeffects of the temporary neural block, and/or creating a substantiallylong term neural block depending on the monitoring.

In aspects, a guidewire in accordance with the present disclosure mayinclude one or more electrodes, each electrode configured to sense,stimulate, and/or ablate a local anatomical site within a body. Inaspects, the guidewire may include a plurality of ablation electrodesconfigured to interface with a wall of a lumen into which the guidewireis placed, so as to provide coupling for delivery of radiofrequency,and/or microwave frequency energy into the wall of the lumen and/ortissues surrounding the lumen, as part of a procedure in accordance withthe present disclosure. In aspects, the guidewire may be configured tomonitor one or more physiologic aspects in conjunction with the energydelivery process (e.g. before, during, after, etc.).

In aspects, a system in accordance with the present disclosure mayinclude a delivery catheter including one or more electrodes, and aguidewire including one or more electrodes, the system configured topass energy between the catheter electrode(s) and the guidewireelectrode(s) as part of a procedure. In aspects, the system may beconfigured to monitor electrophysiological activity between theguidewire electrode(s) and the catheter electrode(s) as part of aprocedure.

In aspects, a guidewire in accordance with the present disclosure mayinclude a drug eluting region (e.g. over an electrode, at the distaltip, etc.), configured so as to elute a drug into the vicinity of theregion during a procedure (e.g. so as to minimize clotting, minimizedamage to adjacent structures, etc.).

In aspects, a guidewire in accordance with the present disclosure mayinclude a thrombus net coupled to the distal tip thereof. The thrombusnet may be configured so as to bridge a cross section of a lumen intowhich the guidewire is placed during a procedure. The thrombus net maybe configured to capture debris generated at a site along the system,guidewire, associated catheter, etc. during a procedure in accordancewith the present disclosure. The thrombus net may be configured so as towithdraw any captured debris along with the guidewire during withdrawalfrom the body.

In aspects there is provided a guidewire for monitoringelectrophysiological activity in the vicinity of an anatomical site ofinterest within the vicinity of a lumen within a body, the guidewireincluding an elongate body dimensioned for insertion into the lumen, anda sensing tip electrically and mechanically coupled to the elongatebody, configured to interface with the wall of the lumen, the sensingtip configured to convey one or more electrophysiological signalsassociated with the activity.

In aspects, the sensing tip may include one or more sensors and/orelectrodes each in accordance with the present disclosure. The sensorand/or electrode dimensioned and configured to interface with theanatomical site of interest upon placement thereby.

In aspects, the sensing tip may include one or more sensors configuredto measure one or more electrophysiological signals related to one ormore of water concentration, tone, evoked potential, remote stimulationof nervous activity, an electromyographic signal [EMG], amechanomyographic signal [MMG], a local field potential, anelectroacoustic event, vasodilation, vessel wall stiffness, musclesympathetic nerve activity (MSNA), central sympathetic drive, tissuetone, nerve traffic, combinations thereof, or the like.

In aspects, a sensing tip in accordance with the present disclosure maybe dimensioned for placement into the parenchyma of an organ coupledwith the lumen (e.g. into a liver, a prostate, a pancreas, a spleen, abladder, a prostate, a ganglion, a gland, into a renal cortex of akidney, an adrenal gland, an adrenal medulla, an adrenal cortex, and/ora renal pelvis of a kidney, combinations thereof, or the like).

In aspects, the sensing tip may be configured such that the sensorand/or the electrode included therein may be substantially isolated froma fluid within the lumen upon deployment of the sensing tip within thelumen, maintains contact with a wall of the lumen during a procedureupon deployment of the sensing tip within the lumen, substantiallymaintains contact with the wall of the lumen while the sensing tip isdragged along the interior thereof, after deployment of the sensing tipwithin the lumen, and/or may be embedded into a wall of the lumen upondeployment of the sensing tip within the lumen.

In aspects, the guidewire may be coupled to a second surgical device,the second surgical device configured to perform an ablation, stress,and/or stimulation procedure within the body.

In aspects, the second surgical device may include a reference electrodeelectrically coupled with one or more of the sensors and/or electrodesincluded within the guidewire.

In aspects, a guidewire in accordance with the present disclosure mayinclude a microcircuit coupled to the sensing tip, configured to conveyone or more sensed physiologic signals to a proximal end of theguidewire, to condition the signal, to perform a digital conversion ofthe signal, to multiplex signals from a plurality of sensors and/orelectrodes within the guidewire.

In aspects, a guidewire in accordance with the present disclosure mayinclude one or more electrodes electrically and mechanically coupledwith the elongate body, configured to deliver energy to the anatomicalsite of interest upon placement thereby.

In aspects, the guidewire may include one or more microneedles slidinglycoupled with the elongate body, configured so as to be deployed beyondthe elongate body into the anatomical site of interest upon placementthereby. Such a microneedle may include a lumen through which asubstance may be delivered to the anatomical site of interest upondeployment of the microneedle there into. Some non-limiting examples ofsubstances include a neurotoxin, a cancer treating agent, aneuroblocking agent, a neurostimulating agent, a neurodepressant, avasodilator, a vasoconstrictor, glucose, insulin, a combination thereof,a formulation of the substance with a delivery vehicle, or the like.

In aspects, one or more of the microneedles may include one or moreelectrodes for sensing, stimulating, and/or ablating the anatomical siteof interest upon deployment of the microneedle there into.

According to aspects there is provided, use of a guidewire in accordancewith the present disclosure, to monitor electrophysiological activity inthe vicinity of a vessel, an artery, a vein, a renal artery, or ahepatic artery, or the like.

According to aspects there is provided, use of a guidewire in accordancewith the present disclosure to monitor electrophysiological activity inthe parenchyma of an organ, a kidney, a renal cortex, a gland, anadrenal gland, a liver, a pancreas, a spleen, a prostate, or a renalpelvis, an arteriole, venule, or vesicle associated therewith, or thelike.

According to aspects there is provided, use of a guidewire in accordancewith the present disclosure to perform and/or monitor a neuromodulationprocedure.

According to aspects there is provided, use of a guidewire in accordancewith the present disclosure, to evaluate a sympathetic and/orparasympathetic activity level associated with an organ, a processassociated with the organ, or a region thereof within a body.

According to aspects there is provided, a system for neuromodulating ananatomical site in the vicinity of a lumen, including a subsystemconfigured to perform a surgical procedure on the anatomical site, aguidewire in accordance with the present disclosure, configured tomonitor electrophysiological activity within the parenchyma of an organcoupled to the lumen and to generate one or more signals therefrom, anda control unit configured to accept signals from the guidewire, and toadjust the surgical procedure dependent upon the signals, to display thesignals (e.g. to an operator, a subject, a client, etc.), to evaluatethe surgical procedure dependent upon the signals, to plan a surgicalpath dependent upon the signals, and/or to determine the extent of theprocedure dependent upon the signals, or the like.

In aspects, the surgical procedure may comprise an ablation, anexcision, a cut, a burn, a radio frequency ablation, radiosurgery, anultrasonic ablation, a cryoablation, an abrasion, a biopsy, delivery ofa substance, a combination thereof, or the like.

In aspects, the system may include a stimulation and/or ablationelectrode configured so as to convey a pulsatile and/or radio frequencysignal to the anatomical site from the control unit, the guidewireconfigured to convey one or more feedback signals related to thepulsatile and/or radio frequency signals back to the control unit. Suchfeedback signals may be related to electrode impedance, a bioimpedance,a local electrical field, or an electrophysiological response to thepulsatile and/or radio frequency signal, or the like. In aspects, thestimulation and/or ablation electrode may be included within theguidewire and/or a sensing tip thereof.

In aspects, the subsystem may be situated coaxially with the guidewirein the lumen.

In aspects, the system may include a sensor to measure one or morephysiologic signals associated with a body comprising the lumen, and toconvey the physiologic signals to the control unit for use in theprocedure. The sensor may be configured to measure one or more of waterconcentration, tone, blood oxygen saturation of local tissues, evokedpotential, stimulation/sensing of nervous activity, electromyography,temperature, blood pressure, vasodilation, vessel wall stiffness, musclesympathetic nerve activity (MSNA), central sympathetic drive, tissuetone, blood flow, a blood flow differential signal, blood perfusion,pupil dilation, electrolyte levels in a biofluid, a blood analyte level,nerve traffic, a combination thereof, or the like.

According to aspects there is provided, a method for evaluatingsympathetic tone of a subject including, recording electrophysiologicalsignals from a lumen and/or from one or more sites within an organ ofthe subject, and generating a metric relating to sympathetic tone fromthe recorded signals.

In aspects the recording may be at least partially facilitated by aguidewire in accordance with the present disclosure.

The method may include applying a stress test to the subject during therecording. The stress test may include having the subject perform avalsalva maneuver, a tilt table test, elevating one or more legs,transient sitting to standing exercises, execute a change in posture,move from a prone position to a sitting or standing position, a breathhold technique, or combinations thereof. In aspects, the stress test mayinclude injecting into the subject a vasodilator, a vasoconstrictor, aneuroblocker, a neurostimulant, a diuretic, insulin, glucose,beta-adrenergic receptor antagonist, angiotensin-ll converting enzymeinhibitor, calcium channel blocker, an HMG-CoA reductase inhibitor,digoxin, an anticoagulant, a diuretic, a beta blocker, an ACE inhibitor,a steroid, combination thereof, or the like. In aspects, such aninjection may be made into the lumen and/or into the organ. In aspects,the injection may be performed at least in part by a guidewire inaccordance with the present disclosure.

In aspects the metric may be generated from recordings taken while thesubject is awake or asleep, assessment while awake versus underanesthesia, before, during and/or after electrostimulation at one ormore sites on the subject, combinations thereof, or the like. Inaspects, the stress test may include having the subject perform aphysical activity, altering the blood volume of the subject, alteringthe heartbeat of the subject, injecting a quantity of saline into thesubject, or a combination thereof.

In aspects, the method may include evaluating how the activity respondsto the stress test, comparing the response to a previous stress testperformed on the subject, comparing the response to a population averageresponse to the stress test, comparing aspects within a single stresstest, comparing the activity before and after a procedure, comparing theactivity between a resting state and an active state, comparing activitybetween an awakened state and a sleeping state, or combinations thereof.

In aspects, the method may include neuromodulating one or moreanatomical sites within the subject.

The method may include inserting a balloon catheter into a lumen coupledto the organ and temporarily blocking the lumen, applying a polarizingpotential to one or more sites in the organ and/or the lumen wall,monitoring another physiologic parameter remotely from the lumen togenerate a corrective signal and using the corrective signal to removemovement artifacts from the electrophysiological signals, stimulatingone or more anatomical sites in the subject during the recording, and/ordiagnosing a medical condition based at least in part upon the metric.

According to aspects there is provided, a method for determining theproperties of one or more neurological features in the vicinity of oneor more monitoring sites, including monitoring one or more of waterconcentration, tone, blood oxygen saturation of local tissues, evokedpotential, stimulation/sensing of nervous activity, electromyography,temperature, blood pressure, vasodilation, vessel wall stiffness, musclesympathetic nerve activity (MSNA), central sympathetic drive, tissuetone, blood flow (e.g. through an artery, through a renal artery), ablood flow differential signal, blood perfusion, pupil dilation,electrolyte levels in a biofluid, a blood analyte level, nerve traffic,or combinations thereof, at one or more of the monitoring sites togenerate one or more physiologic signals, applying a stress test to thesubject, and evaluating the physiologic signals obtained from eachmonitoring site to determine an anatomical map therefrom, a physiologicresponse to the stress test, or the like.

The method may include using the anatomical map or physiologic responseto selectively ablate one or more of the sites.

The method may include determining if a monitoring site includessubstantially more sympathetic or parasympathetic neurological features,and/or applying energy in the vicinity of the lumen so as to induce aneurological block in the vicinity thereof. In aspects, the method mayinclude comparing the physiologic signals obtained before theneurological block to those obtained during the neurological block todetermine the influence of the neurological block there upon, andoptionally determining if the neurological block is favorable in termsof treating an underlying disease state in the body. In aspects, themethod may include applying energy in the vicinity of the lumen so as toinduce a substantially permanent neurological block in the vicinity ofselected monitoring sites.

According to aspects there is provided, use of a method in accordancewith the present disclosure for evaluation of the effectiveness of aneuromodulation procedure within a body.

BRIEF DESCRIPTION OF THE DRAWINGS

Several aspects of the disclosure can be better understood withreference to the following drawings. In the drawings, like referencenumerals designate corresponding parts throughout the several views.

FIGS. 1a-d show aspects of a guidewire in accordance with the presentdisclosure.

FIGS. 2a-p show aspects of guidewire tips associated with a guidewire inaccordance with the present disclosure.

FIGS. 3a-d show aspects of a sensing guidewire in accordance with thepresent disclosure coupled with a second surgical tool or system formonitoring locations in a body before, during and/or after a surgicalprocedure.

FIGS. 4a-c show devices in accordance with the present disclosure placedso as to monitor activity within an organ within a body.

FIGS. 5a-d show aspects of a fiber based sensing guidewire in accordancewith the present disclosure.

FIGS. 6a-e show aspects of flexible multi-electrode guidewire tips inaccordance with the present disclosure.

FIGS. 7a-b show a guidewire and surgical device each in accordance withthe present disclosure, positioned within an organ within a body.

FIGS. 8a-c show aspects of a device in accordance with the presentdisclosure configured and dimensioned to interface with a carotid body.

FIG. 9 shows aspects of a multi-tool based approach to monitoring and/orsurgically interacting with a carotid body, in accordance with thepresent disclosure.

FIG. 10 shows aspects of a tool tip for use in a surgical tool inaccordance with the present disclosure.

FIG. 11 illustrates aspects of coordinated multi-tool procedures beingapplied to an organ as well as highlights placement options forstressing an organ during a procedure in accordance with the presentdisclosure.

FIG. 12 shows aspects of a method for assessing an anatomical sitewithin a body.

DETAILED DESCRIPTION

Particular embodiments of the present disclosure are describedhereinbelow with reference to the accompanying drawings; however, thedisclosed embodiments are merely examples of the disclosure and may beembodied in various forms. Therefore, specific structural and functionaldetails disclosed herein are not to be interpreted as limiting, butmerely as a basis for the claims and as a representative basis forteaching one skilled in the art to variously employ the presentdisclosure in virtually any appropriately detailed structure. Likereference numerals may refer to similar or identical elements throughoutthe description of the figures.

According to a first aspect there is provided a controlled nerveablation system, which may include the capability to sense one or morephysiologic parameters at one or more points in the vicinity of asurgical site or within an affected organ, as well as include thecapability to stimulate and/or ablate tissues at one or more of the samepoints and/or an alternative point in the vicinity of a surgical site.The nerve ablation system may be configured so as to access vesselsand/or surgical sites in the body. The non-limiting examples disclosedherein may be directed towards such configurations (e.g. to controllablyprovide neuromodulation procedures to an organ within a body, so as tocontrollably ablate renal nerves along a renal artery via an endoscopicor percutaneous procedure, etc.). Such non-limiting examples are meantto serve as guidance that may be applied to other treatment sites withina body, disease states, etc.

By surgery/surgical is meant, a surgical procedure, an interventionalprocedure, a minimally invasive procedure, and the like.

Some non-limiting examples of medical conditions that can be treatedaccording to the present disclosure include genetic, skeletal,immunological, vascular or hematological, muscular or connective tissue,neurological, ocular, auditory or vestibular, dermatological,endocrinological, olfactory, cardiovascular, genitourinary,psychological, gastrointestinal, respiratory/pulmonary, neoplastic, orinflammatory medical conditions. Further, the medical condition can bethe result of any etiology including vascular, ischemic, thrombotic,embolic, infectious (including bacterial, viral, parasitic, fungal,abscessal), neoplastic, drug-induced, metabolic, immunological,collagenic, traumatic, surgical, idiopathic, endocrinological, allergic,degenerative, congenital, or abnormal malformational causes.

The present systems and methods also encompass enhancing the therapeuticeffects of other therapies, such as methods and systems working inconjunction with a pharmaceutical agent or other therapies to augment,enhance, improve, or facilitate other therapies (adjunctive therapies)as well as reducing/minimize and counteracting side effects,complications and adverse reactions for any therapies involved intreating the above-mentioned medical conditions.

In aspects, one or more functions of a liver may be augmented by atreatment and/or method, and may be monitored, examined, or evaluated(including response to a stress test, resting state, transient change inan analyte, etc.), and/or monitored in accordance with the presentdisclosure include glucose storage/release mechanisms, metabolicsensing/response (and related signal traffic to the brain relatedthereto), glucoregulatory function, afferent vagal activity reaching thebrain, chemoreceptor function (or related signal traffic associatedtherewith), lipid sensing/synthesis, regulation of hepatic insulinsensitizing substance, afferent traffic augmentation associated withglucosensors (e.g. primarily in the region of the portal vein, etc.),protein sensing, GLP-1, leptin, CCK, FFA, PPAR alpha and gamma,glycogenolysis, gluconeogenesis, VLDL secretion, ketogenesis,hypoglucemia sensing, combinations thereof, or the like.

In aspects, one or more guidewires, surgical systems, methods, or thelike each in accordance with the present disclosure may be used toinfluence, and/or treat cancer progression relating to a perineuralinvading cancer, such as cancer of the prostate, pancreas, breast,cervix, ovaries, bladder, or combinations thereof. Such treatments maybe used to treat pain associated with cancer to slow, to reverse, and/orto prevent perineural invasion of a cancerous tumor into a surroundingneural microenvironment to interrupt, decrease, influence themicroenvironment and/or inflammation of tissues in the state of acancerous tumor, and/or stop neural communication to/from a canceroustumor and/or the microenvironment surrounding the tumor to a remote sitewithin a body.

In aspects, a system/surgical tool in accordance with the presentdisclosure may be used to access, monitor, and/or to treat one or moreneurological pathways, ganglia, and/or sensory receptors within a body:Ampullae of Lorenzini (respond to electric field, salinity, temperature,etc.), baroreceptors, chemoreceptors, hydroreceptors, mechanoreceptors,nociceptors, osmoreceptors (osmolarity sensing), photoreceptors,proprioceptors, thermoreceptors, combinations thereof, and the like.Such receptors may be associated with one or more organs and/orphysiologic processes within the body (e.g. a regulatory process, etc.).

In aspects, a surgical tool in accordance with the present disclosuremay take the form of a guidewire. The guidewire may be dimensioned andconfigured for placement within a lumen of a body at and/or beyond asurgical site and/or anatomical site of interest, so as to monitor oneor more physiologic signals near the tip thereof. In aspects, theguidewire may provide a pathway for delivery of a second surgical deviceto the surgical site.

In aspects, a guidewire in accordance with the present disclosure mayinclude one or more energy delivery means for delivering energy to ananatomical site within and/or beyond the wall of a lumen into which theguidewire tip has been placed.

In aspects, a guidewire in accordance with the present disclosure mayinclude one or more sensors (e.g. as located on a micro-tool-tip, aclamp, a hook, a wire element, an electrode in a matrix, etc.) near tothe tip thereof. One or more sensors may include a pressure sensor, atonal sensor, a temperature sensor, an electrode (e.g. to interact witha local tissue site, provide a stimulus thereto, measure a potentialtherefrom, monitor current to/from the tissues, to measure abioimpedance, measure an evoked potential, an electromyographic signal[EMG], an electrocardiographic signal [ECG], an extracellular potentialelectrode, a mechanomyographic signal [MMG], etc.), an acoustic sensor,an oxygen saturation sensor, or the like.

In aspects, a guidewire in accordance with the present disclosure mayinclude one or more analyte sensors, configured to measure one or moreanalyte concentrations or concentration trends before, during, and/orafter a procedure within a body. Such analyte sensors may be provided inan electrochemical form, a fluorescent form, an electro-optical form, aswelling responsive gel, etc.

A sensing guidewire in accordance with the present disclosure may beadvantageous for accessing very small anatomical sites within a body,accessing adjunct arteries and/or arteriole pathways along a bloodsupply to a target organ, accessing a plurality of vessels coupled to anorgan, accessing the parenchyma of an organ, for highly localizedinteraction with a tissue site, for accessing otherwise challenginglumens (e.g. a lumen with substantially small diameter, withsubstantially tortuous shape, etc.). In aspects, a guidewire inaccordance with the present disclosure may provide a means for directingone or more additional tools to a surgical site within a body. Inaspects, a guidewire in accordance with the present disclosure may beconfigured to sense physiologic parameters from and/or to treat tissueswithin such miniature lumens as part of a procedure (e.g. a surgicalprocedure, a diagnostic procedure, an ablation procedure, etc.).

In aspects, one or more of the sensors included on the guidewire andelectronics associated therewith may be configured to elucidate a rangeof key physiologic aspects during a procedure. The following descriptionoutlines some non-limiting approaches in this respect.

Bioimpedance between one or more electrodes situated on the surgicaltool (and optionally a remote electrode), may be used to determine thedegree of contact between one or more of the electrodes and an adjacentanatomical site, a tissue state near to one or more of the electrodes,water content of tissues in the vicinity of one or more of theelectrodes, and/or potentially estimate the bias force between theelectrode and the anatomical site. Additionally, alternatively, or incombination, bioimpedance measurements between one or more electrodesmay be useful in determining when adequate contact has been made withthe wall of lumen against which the sensor has been biased as well ashow much current may be applied to an anatomical site during a surgicalprocedure (e.g. ablation, RF ablation, etc.). Additionally,alternatively, or in combination bioimpedance between one or moreelectrodes may be used to determine the status of tissue positionedthere between. In aspects, the bioimpedance spectrum between two or moreelectrodes arranged along the surgical tool or between coordinatingtools may be used to map the local tissue impedance. Such informationmay be useful to elucidate where such tissue has been completelyablated, where tissue has yet to be ablated, etc.

In aspects, bioimpedance measurements may be correlated with nervedamage data, obtained during prior surgeries, during development of theprocedure, and/or obtained during specific testing procedures, such thatchanges in local bioimpedance data may be used during a surgicalprocedure to determine the extent of the ablation procedure. Such aconfiguration may be advantageous in the case that the surgicalprocedure itself overwhelms the local electrophysiological activity tothe extent that neurological monitoring may be hindered for a prolongedperiod of time after the procedure has been completed.

Mechanomyographic information may be obtained from one or more sensingtips in accordance with the present disclosure during a procedure asdetermined by slight changes in an associated strain measurement, tipvibration, and/or contact force measurement (e.g. via direct forcemeasurement between the tip and the local anatomy, and/or via changes inthe deformation of the surgical tool tip as measured by an associatedmicro strain gage attached thereupon). Mechanomyographic information maybe related to local nervous activity either naturally occurring or inresponse to a stimulus (e.g. optionally applied by one or more sensorytips, locally, remotely, during and/or via a local RF pulse, etc.). Thetip of a surgical device in accordance with the present disclosure maybe equipped with a piezoresistive strain gauge, a piezoelectricmicrotransducer, an interfacial pressure sensing membrane or the like todetect mechanomyographic signals. In aspects, the surgical tool tip maybe coated with a micro or nano coating of a piezoresistive and orpiezoelectric material (e.g. a piezoelectric polymer, an electret, anano-particulate filled elastomer, etc.). In aspects, themechanomyographic tip may be configured so as to measure one or moreaspects of the tissue compliance of the local tissues (e.g. so as toidentify calcified material, cancerous tissues, etc.).

In aspects, electrophysiological monitoring at or between one or moreelectrodes integrated into the surgical tool, may be used to monitorand/or to map nervous response, electromyographic response (EMG), evokedpotential, single or multi-unit neural traffic, etc. along the wall ofthe local anatomy (e.g. vessel wall, the outside of a vessel wall,within an associated tubule, ureter, artery, vein, arteriole, venule,within the parenchyma of an organ, etc.). Such information may beadvantageous for selecting tissues on which to perform a surgicalprocedure (e.g. an ablation procedure, a biopsy, a drug deliveryprocedure, a selective ablation procedure, etc.), to follow and/or map anerve along the length of the surgical site (e.g. along the wall of anartery, a vein, a tubule, etc.), to monitor electrophysiologicalfunction before, during, and/or after a surgical procedure, or the like.In aspects, local electric field potentials (EFP) may be monitoredbefore, during and/or after a surgical procedure as a means formonitoring local nervous activity. Thus EFP signals may be used asfeedback for monitoring the extent of a denervation procedure.

In aspects, one or more electrodes may be configured to monitor localelectrical fields during an ablation procedure in order to betterdetermine the current flow path through the adjacent anatomy, connectedto a warning system to indicate to an operator when the ablation fieldis insufficient for achieving the intended goal, etc. Such aconfiguration may be advantageous for avoiding unnecessary damage to thetissues during a misfired ablation session, etc.

In aspects, the tone (e.g. mechanical properties, wall stiffness,elastic spectral response, mechanical impedance, physiologic properties,etc.) of the adjacent tissues may be determined by combining strainand/or force measurement of sensors integrated into the surgical toolwhile applying movement (optionally cyclical or oscillatory movement) toone or more sensor tips while biased against the adjacent tissues. Sucha surgical tool may include means for applying a local excitation (e.g.such as by a local piezoelectric transducer, a capacitive transducer, anelectrochemical transducer, etc.) to one or more of the sensors orglobally (e.g. such as by transverse oscillations, axial oscillations,general oscillations of the surgical tool tip, the clamp, the hook, theloop, etc.).

In aspects, one or more surgical tool tips may be interfaced with theassociated tissues at an acute angle. By acute angle is meant such thatthe surgical tool tip approaches the associated tissue surface at anangle other than perpendicular thereto. A local excitation may beapplied with relatively small amplitude so as not to generatesubstantial relative movement between the tissue and the tip during theexcitation process (e.g. such that the transverse contact forces remainbelow the slip conditions between the tip and the tissue, such that theymove together during excitation). By relatively small is meant anexcitation that is sufficiently small in amplitude such that the sensingtip may not appreciably slide along the tissue surface. In aspects, avibratory exciter included in the sensory tip, or in a structureattached thereto, may be configured to generate the excitation.

Such a tone monitor may be combined with interfacial contact sensingand/or sensor tip strain measurement in order to generate a wealth oflocal tissue information during a surgical procedure. In aspects, thelocal tissues may stiffen during an ablation procedure. By monitoringlocal tissue tone, a stiffness level may be used to characterize when asuitable degree of ablation has been applied so as to irreversiblydamage the tissues. Monitoring of a local tissue tone at a monitoringsite significantly removed from the surgical site such that the surgicalprocedure does not directly affect tissues in the vicinity of themonitoring site (e.g. does not directly cut, heat, ablate, abrade, thetissues, etc.) may also be advantageous for determining an effect of thesurgical procedure on one or more physiologic parameters of a tissue(e.g. a vessel wall stiffness, change in nerve activity, change in localblood perfusion, etc.) adjacent to the monitoring site.

Such tone measurement may be useful in determining the local stiffnessof tissues (and/or overall wall stiffness of an adjacent vessel, organ,etc.) in contact with an array of surgical tool tips (e.g. so as todetermine the type of tissue adjacent to one or more tips, to locatetransitions between one tissue type and another, to locate regions ofexcessive wall thickness, to locate a cancerous tumor, etc.). Tonemeasurement may further be used to characterize the type of tissue withwhich the tip is interfacing (e.g. muscle, nervous tissue, plaque,cancerous tissue, etc.). Such information, possibly in combination withbioimpedance data, may be used to determine how much RF energy to applylocally during an RF ablation procedure.

In aspects, relating to a method for RF ablating tissue, the localtissue tone may be measured before, during, between individual RFpulses, and/or after a train of RF pulses. As the local tissue tonechanges during application of the RF pulses, the tonal changes may beused to determine the extent of the therapy. As the RF ablation processis applied to the adjacent tissues (via one or more sensing tips, anablation electrode, etc.), the tonal measurements (as determined by oneor more sensing tips, via the same tip through which the RF signal maybe applied, etc.) may be monitored as the tonal measurements may not besignificantly affected by the local RF currents.

Electrophysiological stimulation and/or sensing from one or moreelectrodes arranged along the surgical tool may be used to monitorand/or stimulate nervous and/or physiologic function within a localanatomical structure (e.g. a vessel wall, along a nerve, an organ wall,a duct, etc.). Such information may be used to hunt for target tissues(e.g. nerves), select tissues for a surgical procedure, to determine thedegree of progression of a surgical procedure (e.g. a degree of ablationor neuromodulation during surgery, etc.). In aspects, directionalstimulation and sensing may be used to selectively treat only nervesthat are configured to send signals in the preferred direction (e.g. toselectively target primarily efferent nerve bundles, afferent nervebundles, etc.).

In aspects, one or more of the electrodes may be configured toapply/receive an RF or microwave current to/from the surrounding tissue.The current may be provided locally between two or more electrodes, oralternatively between one or more electrodes and a macroelectrode placedelsewhere on the body (e.g. on a large skin patch over the surgicalsite, an electrode placed on another organ, as selected from multiplepatches placed over the body, in an associated catheter electrode,etc.). In a non-limiting example where current is restricted to beingapplied between electrodes, the path for current flow may be wellcontrolled, yet may be highly localized. Alternatively, in an examplewhere current is passed between one or more electrodes and one or moreremotely situated macroelectrodes, the current flow may be morechallenging to control, but may be used to access tissues more remotefrom the surgical tool (e.g. farther into the adjacent tissues, etc.).

In aspects, network impedance measurements between one or moreelectrodes and one or more macroelectrodes (e.g. as attached to the bodyof the patient), may be monitored prior to and/or during application ofan RF ablation current. Each surgical tool electrode and/ormacroelectrode may include an impedance control circuit that may beadjustable such that the overall current flow through the network formedfrom all the elements is controlled there through. Such a configurationmay be advantageous to better control the local ablation process, thustargeting the local tissues with more accuracy and confidence than lesscontrolled approaches.

In aspects, a plurality of electrodes may be engaged with the flow ofcurrent during an ablation process. In such a non-limiting example, thelocal impedance of each pathway (i.e. through the surgical tool and eachassociated electrode) may be monitored and/or controlled so as to betteroptimize the current delivered thereto. Additionally, alternatively, orin combination, the local current flow through each electrode may bemonitored so as to determine the path of the current flow, to ensure noleakage currents are detected, etc. Such information may be used tobetter control the delivery of ablation and/or stimulation currents tothe local anatomy during an ablation/stimulation procedure.

Optionally, before, during and/or after the ablation or stimulationcurrent is applied to the surrounding tissues, one or more sensorsarranged on the surgical tool may monitor a physiologic parameter (e.g.water concentration, tone, blood oxygen saturation of local tissues,evoked potential, stimulation/sensing of nervous activity, EMG,temperature, analyte level, etc.) to determine the extent of completionof the intended surgical procedure.

In aspects, the tip of the surgical tool may be equipped with an opticalmicrosensor (e.g. a micropackage including a light source and/or acomplementary metal-oxide semiconductor (CMOS) photosensor). During asurgical procedure, the optical microsensor may be positioned against ornear to the local tissues for analysis before, during and/or after anablation procedure.

In aspects, an optically configured sensor (or group of tips) may beconfigured to locally assess blood perfusion, renin concentration,tissue colorimetric properties, and/or blood oxygenation in the tissuesadjacent thereto. The system may be configured to automatically adjustand/or halt the surgical procedure based upon changes (or lack thereof)in this signal. Alternatively, additionally, or in combination, thesystem may alert a user (e.g. a surgeon, an attendant, etc.) to a changein this signal before, during, and/or after a surgical procedure. Such aconfiguration may be useful for assessing local tissue health before,during, and/or after a surgical procedure.

In aspects, one or more optically configured sensors may be configuredto monitor for changes in the colorimetric properties of tissuesadjacent thereto, such as during an ablation procedure. Suchcolorimetric property changes may be indicative of a change in tissuestate caused by the procedure (e.g. local tissue damage, denervation,etc.).

In aspects, one or more optical sensors may be configured so as to bebiased towards the tissues of the vessel in the vicinity of the surgicalsite or distally therefrom. The optical sensors may include one or morelight sources (e.g. light emitting diodes, fiber optic tips, etc.)configured to delivery narrow, multiband, and/or wideband light to theadjacent tissues. The optical sensors may include one or morephotodetectors (e.g. a photodetector, a phototransistor, OCT fiberbundle, a fiber optic tip, etc.) to receive and/or analyze the lightreflected from the adjacent tissues. The received light may be relatedto that emitted by one or more of the light sources, or may be receivedfrom an ambient light source, located to the exterior of the vessel, orthe exterior of the subject's body.

In aspects, one or more of the sources may be configured to emit lightat predetermined wavelengths such that different absorptioncharacteristics of the adjacent tissues, dependent on the wavelengths,may be observed during the surgical procedure. The photodetectors may beconfigured to receive at least a portion of this light, so as to assessthe absorption characteristics with the system (e.g. via apre-amplification system in accordance with the present disclosure, inan attached electronics unit, etc.). The photodetected signals may beused to determine an oximetry value or a signal related thereto.

In aspects, the optical sensors may be biased towards a site on thelumen wall before, during, and/or after the surgical procedure.Alternatively or in combination, the optical sensors may be held in apredetermined orientation with respect to the lumen wall (such as viabeing attached to a collar of known size, attached to a structure ofknown width, as part of a structure that is expanded to a known radius,onto the inner surface of a hook element, etc.). The bias between thesensors and the wall may be controlled by sensors and actuators both inaccordance with the present disclosure. Changes in the optical signalsdetected by the photodetectors (due to changing bias force) before,during and/or after a surgical procedure may be related to changes inthe bias force with which the sensors are held against the vessel wall.Such a configuration may be advantageous for determining a change insympathetic tone and/or vasodilation before, during and/or after asurgical procedure.

In aspects, one or more of the optical sensors may be coupled with oneor more strain and/or interfacial force measurement methods, to give amore precise reading of the bias force between the sensing tip(s) andthe adjacent tissues.

In aspects, the optical sources may be selected such that thepenetration of the light into the adjacent tissues may be controlled. Inaspects, a blue wavelength and a red wavelength may be emitted into thetissues. The blue wavelength may provide information relating to thedeformation and absorption near the to the surface of the tissues, whilethe red wavelength may penetrate more deeply into the adjacent tissues,providing a signal that changes in response to deformation of tissuesfarther from the contact site(s) between the sensor(s) and the tissue.The photodetectors or equivalent optical detection pathway may includefilters, polarized windows, or the like to separately assess thedifferent spectra during an analysis. Comparison between thephotodetected signals in the blue spectrum with those obtained from thered spectrum may be used to determine tone and/or elastic modulus of thetissues of the vessel in the vicinity of the optical sensors. Such aconfiguration may be advantageous for assessing sympathetic tone and/orvasodilation, vessel wall stiffness, and/or local tissue stiffnessbefore, during and/or after a surgical procedure. Changes in suchproperties may be indicative of the degree of completion of the surgicalprocedure.

In aspects, an externally placed (e.g. onto the body of the subject)energy source (e.g. infrared, near infrared, visible, microwave,radiation, etc.) may be directed into the body towards the surgicalsite. The energy source may optionally be modulated to provide a moreeasily detected signal within the subject. One or more optical sensorsarranged upon the surgical tool may be configured to sense light emittedfrom the energy source. The mapping of received light may be used tolocate anatomical features such as nerves near to one or more of theoptical sensors.

One or more externally placed light sources may be used to help locatethe anatomical sites of interest during the procedure. An external lightsource may include a narrow band light source, a broad band lightsource, light sources spaced apart from each other, and/or combinationsthereof. The light sources may be modulated so as to be more easilydetectable by sensors located in or near to the anatomy of interest. Inone non-limiting example, a plurality of light sources may be aimed atthe surgical site from distinct vantage points within the body (i.e. asaccessed via an endoscopic procedure, etc.) or externally to the body(i.e. as positioned at locations on the body).

In aspects, an endoscopic camera may be placed near to the anatomyduring a procedure to observe both the anatomy, as well as placement ofthe surgical tools in the vicinity of the anatomy. In one non-limitingexample, the endoscopic camera and/or light source may provide asuitable macroelectrode for RF ablation processes performed during thesurgical procedure.

In aspects, one or more optical sensors may be equipped with acorresponding micro-light source (e.g. an organic light-emitting diode(oLED), a light-emitting diode (LED), etc.). The micro-light source maybe used to direct light into the adjacent tissues. One or more opticalsensors may be configured to detect light emitted from the micro-lightsource as back scattered by the adjacent tissues. Such information maybe used to detect anatomical features (e.g. nerves, tumors, etc.) in theadjacent tissues.

Such optical configurations may be advantageous for mapping the localtissues before, during and/or after a surgical procedure. They may alsobe advantageous for implementation into a nerve detection system (e.g.as input to a nerve hunting algorithm, etc.).

In aspects, the surgical tool may include one or more microcircuitsinterconnected with one or more of the sensors. Such a microcircuit mayinclude signal processing circuitry, a local control circuit,multiplexors, communication hardware, power management, combinationsthereof, or the like. In order to substantially reduce the number ofsignal wires that must be routed to the surgical site during theprocedure, a networked array of electrodes arranged within the surgicaltool may be multiplexed together with a locally placed control circuit(e.g. an application specific integrated circuit,distributed/interconnected circuit elements, a collection of flexiblesemiconducting circuit elements, etc.). The control circuit maycommunicate such signals with an extracorporeal system (e.g. a computer,a control system, an RF ablation controller, a data acquisition system,etc.). The control circuit may communicate with the extracorporealsystem via analog and/or digital methods. In one non-limiting example,the communication may be of primarily digital means such that thecontrol circuit may exchange data pertaining to any sensing tip in thearray, as well as switch data, control data, RF pulse routing, etc.

In aspects, the networked array of electrodes may be interconnected withdistributed electronic elements and flexible electrical interconnects(e.g. as applied to a clamp surface, a hook, a loop, as provided bystructural wires, microfingers, wire mesh elements, etc.).

A surgical tool (e.g. a guidewire, a catheter, etc.) in accordance withthe present disclosure may include one or more microfingers arrangedsuch that each microfinger may move or interact with local anatomysubstantially independently from other microfingers in the tool. Thus ifan array of microfingers is placed against a rough or otherwiseuncontrolled surface, each microfinger may be able to contact, andsubstantially maintain contact with the surface during use, even if themicrofinger array is dragged along the surface during a procedure. Suchindependently adjustable microfingers may be advantageous so as tomaintain a known interfacial pressure, especially while monitoring,stimulating and/or ablating the tissue with the microfingers.

By microfinger is meant a, potentially curved, finger like member (i.e.optionally with multi-axial curvature). Such microfingers may generallyhave a characteristic width (although may be of any cross sectionalmakeup). The microfingers may generally have characteristic widths onthe order of approximately 1 mm, 0.5 mm, 0.1 mm, 0.05 mm, 0.01 mm, orthe like. In aspects, one or more microfingers may include a nitinolstructure (e.g. a wire, a ribbon, etc.) with characteristic width ofapproximately 50 μm.

In aspects, one or more of the microfingers may be selectively coatedwith an isolation layer (e.g. an oxide layer, a dielectric coating, apolymer layer, a lubricious layer, etc.). Such isolation may beselectively applied to regions of the microfingers (i.e. so as to createisolated regions and sensitive regions thereof).

The microfingers may be configured so as to bias against the adjacenttissues during a procedure and may be used to sweep the local anatomy,both sensing and ablating during a surgical procedure. The microfingerdimensions and structure may be designed so as to provide substantiallyuniform and predictable bias forces on the adjacent tissues over a widerange of movements and dimensional variation.

In aspects, one or more microfingers may include a spring-like wireelement (e.g. nitinol, spring steel, etc.) or may include compositestructures including a spring-like element to provide a bias force so asto push the tip of the microfinger towards the wall of a vessel, anorgan, and/or a tissue site of interest.

In aspects, a microfinger may include a nitinol structure, optionallyconfigured for passage of current flow, to and from the surroundingtissues. The nitinol structure may be configured such that, when an RFpulse is applied there through towards the surrounding tissues, thenitinol structure may retreat from the tissues after a predeterminedamount of energy has passed there through. Thus the nitinol structuremay provide an inherently controlled method for applying a bolus of RFenergy to the surrounding tissues. Such a configuration may be adaptedfor use simultaneously, additionally, alternatively and/or incombination with the other aspects described in this disclosure.

In aspects, one or more of the microfingers may be formed slightly offaxis, such that relative axial movement of an overlying sheath may beused to retract the microfingers into the sheath or deploy themicrofingers outwards so as to interface with the anatomical site.

Such a configuration may be advantageous for simultaneously mapping andselectively ablating an anatomical site during a surgical procedure.

In aspects, one or more microfingers may be provided with highlyminiaturized and flexible structure so as to more easily access hiddenand/or difficult to access anatomical sites within the body.

In aspects, one or more of the microfingers may include a sensor inaccordance with the present disclosure for capturing information from anadjacent anatomical site.

In aspects, a system in accordance with the present disclosure mayinclude a coolant delivery system (e.g. a saline delivery system) inorder to cool the microfingers and/or surrounding tissues during and/orafter an ablation procedure. Such coolant delivery may be advantageousfor minimizing char and excessive damage associated with an ablationprocedure. In aspects, such a coolant may be provided to maintain one ormore of the microfingers in a first state (i.e. a delivery state). Whenthe coolant flow is stopped, the associated microfingers may transitionto a second state (i.e. a deployed state). Such a configuration may beadvantageous for delivering a guidewire tip in accordance with thepresent disclosure deep into a target lumen before deploying one or morezones of the guidewire so as to interface with the walls of the lumen aspart of a procedure.

In aspects, one or more of the microfingers may include an exposedelectrode area arranged so as to primarily interface with the walls ofthe adjacent anatomy upon deployment. Such a configuration may beadvantageous for minimizing current flow into the adjacent tissues andto better control RF current flow in the vicinity of the electrodes,etc.

The microfingers may include one or more active material elements.Control signals delivered to the active material element may help tobias the microfingers towards the intended surgical site, activelycontrol the contact forces between finger tips and the surgical sites,etc. Some non-limiting examples of active materials that may be suitablefor application to one or more microfingers include shape memorymaterials (e.g. shape memory alloys, polymers, combination thereof),electroactive polymers (e.g. conjugated polymers, dielectric elastomers,piezoelectric polymers, electrets, liquid crystals, graft elastomers,etc.), piezoceramics (e.g. amorphous piezoceramics, single crystals,composites, etc.). In addition the active material may be used as avibratory exciter and/or mechanical probe, for use in monitoring thetone of the adjacent tissues (see above), alternatively, in addition orin combination, to cause vibratory/ultrasonic ablation and/or localheating to the tissues. In aspects, such active material elements may beconfigured for simplified deployment of one or more aspects of anassociated guidewire towards the walls of a lumen into which it isinserted during a procedure.

In aspects, one or more electrodes may include a conjugated polymer tointerface with the adjacent tissues. Some non-limiting examples ofsuitable conjugated polymers include polyaniline, polypyrrole,polyacetylene, poly(3,4-ethylenedioxythiophene), and the like.

In aspects, one or more of the microfingers may include an electricalshield such that the associated microfinger tips are effectivelyshielded from other currents flowing through an associated surgical tool(such as a catheter), the body, etc. during a procedure.

In aspects, a surgical tool may include or interface with abi-directional switching network, microcircuit amplifier array, etc. inorder to amplify sensed signals as close as possible to the anatomicalinterface, as well as to switch the function of a microfinger tipbetween sensory, stimulatory, and/or ablation functions, etc.

A bidirectional switching network may be used to enable multi-functionalstimulation/sense capabilities in one or more microfingers, tool tips,etc. The switching network may be included in a local amplifier array,included in a flexible circuit on one or more microfingers, attachedalong the surgical tool, as part of the electrical routing along afinger, etc. or alternatively as an extracorporeal element included in asurgical system in accordance with the present disclosure.

A micro amplifier array may be used to preamplify the signals obtainedfrom one or more sensory aspects of the microfingers, so as to improvethe noise signature, etc. during use.

In aspects, one or more of the microfingers may be provided such thatthey are sufficiently flexible so as to buckle, or change orientationduring back travel (e.g. configured and dimensioned so as to prolapse),so as to prevent puncture of the local anatomy. A configuration asoutlined in this example may be advantageous for providing contact withthe local anatomy without significant risk of damaging the adjacentanatomy (e.g. puncturing a vessel wall, etc.) which may be a concernwith stiffer, more traditional structures.

In aspects, one or more of the microfingers may be sufficiently hyperelastic (e.g. formed from a memory alloy material, a superelasticmaterial, etc.) so as to effectively deploy from a very small deploymenttube and expand outward to larger tissue areas over which to monitor.Such a configuration may be advantageous in so far as a small number ofunit sizes may be suitable for treating a wide range of anatomicalstructures. In addition, the designed curvature and form of amicrofinger may be substantially chosen so as to further enable a widedeployable range of movement.

In aspects, a surgical tool including a plurality of microfingers inaccordance with the present disclosure may be employed so as todetermine physiologic response more remotely from an intended surgicalsite than may be available within a single array. Any of the aboveconcepts may be employed along the same lines by extending interactionsbetween microfingers within an array, to inter-array interactions.

A system in accordance with the present disclosure may be used tomonitor physiologic activity associated with a surgical site prior to,during and/or after a surgical procedure is applied thereto. In aspects,a system in accordance with the present disclosure may be configured toprovide a surgical procedure, optionally in conjunction with themonitoring. Some suitable examples of surgical procedures include RFablation, Argon plasma coagulation, laser ablation, water jet ablation,ultrasonic ablation, cryoablation, microwave ablation, abrasion, biopsy,delivery of a substance (e.g. a chemical, a drug substance, an acid, abase, a chemotherapy drug, etc.), etc. The local physiologic activity(e.g. nervous activity, blood perfusion, tonal changes, muscularsympathetic nerve activity, local field potentials, etc.) may bemonitored with one more sensors and/or associated stimulators.Additionally, alternatively, or in combination, a technique forassessing the properties of an associated surgical site may be employed.Such techniques may include assessing values and/or trends inbioimpedance, blood pressure, tissue oxygenation, tissue carbon dioxidelevels, local temperatures and changes thereof, etc.

In aspects, the system may be configured to deliver a substance such asa therapeutic agent (e.g. a neuroblocking agent, ethyl alcohol,botulinum toxin, etc.) to the anatomical site of interest or a treatmentsite.

In aspects, a system in accordance with the present disclosure mayinclude a substrate onto which one or more sensors may be coupled. Sucha substrate may be formed from a clamp face, a hook interface, a mesh,an interwoven ribbon array, a cloth, rolled film, etc. The substrate mayinclude stretchable and/or flexible electronic materials.

In aspects, one or more electrical interconnects may be formed fromcarbon nanotubes (e.g. single-walled nanotubes (SWNTs), multi-wallednanotubes (MWNTs), etc.), nanowires, carbon fibers, metalized carbonfibers, metallic wires, composites, conductive inks, combinationsthereof, or the like.

A portion, or all of the substrate and/or an associated substratecarrier film may be formed from polyurethane, a silicone, a generalelastomer, silk fibroin materials, or the like and/or combinationsthereof. Inclusion of microporous or fibrous substrates, may beadvantageous to allow the substrate or substrate carrier film to adhereto the adjacent tissues via capillary effects (i.e. tendencies to wickfluid from adjacent tissues into the substrate). The thickness of filmsformed from the material may be less than 30 μm thick, less than 20 μm,less than 10 μm, less than 4 μm, less than 1 μm. Composites of somewhatstiffer materials (such as polyimide, polyethylene terephthalate (PET),polyethylene naphthalate (PEN), etc.) and somewhat softer materials(e.g. silicones, polyurethanes, thermoplastic elastomers, etc.) may beused to compromise between overall structural stiffness and conformalcapabilities.

Patterned overcoats and/or composite layers may also be used to exposeelectrode materials and/or sensing tips to the surrounding tissues inthe vicinity of measurement regions, etc.

In aspects, one or more regions of the substrate may be formed from asilk material (e.g. Bombyx mori cocoons). The material may be processedto remove sericin (which may cause undesirable immunological response)using methods known in the art. The resulting material can be solventcast into shapes and crystallized to form self-supporting structures.

In aspects, adaptive temperature estimation may be used to bettercontrol the RF process. Modeling of changes in local bioimpedance may berelated to local temperature changes during the ablation process. Suchmeasurements as well as local thermoconductive properties, tissuethermoconduction, etc. may also influence the rates at which a localablation process may take place (i.e. as related to a thermal ablationprocess).

The system may also include one or more sensors for monitoring nervousactivity and/or related physiologic activity during the RF ablationprocess. Some examples of suitable monitoring techniques include evokedpotentials, local field potentials (LFP), electromyography (EMG),muscule sympathetic nerve activity (MSNA), mechanomyography (MMG),phonomyography (PMG), and combinations thereof. Mechanomyography (MMG)measures the force created by local muscle contractions caused byassociated neural activity. Phonomyography (PMG) measures low frequencysounds associated with movement generated by associated neural activity.Traditionally, techniques such as MMG and PMG have been employed onexternally accessible nervous and muscular tissues. One advantage ofsuch techniques as provided herein may be that they may not be as easilyaffected by local electrical noise as EMG and the effects of the nervousactivity may be generally sensed farther from the associated nerve thanwith electromyographic techniques.

Alternatively, additionally or in combination the ascribed sensingtechniques may be combined with stimulation from local sources. Suchstimulation and sensing may be advantageous in determining functionalityof local nerves without the need to listen to complex biologicallygenerated nervous activity. Furthermore, combined stimulation andsensing may be advantageous for determining functionality of a localnerve in real-time during a denervation and/or ablation procedure (e.g.the successive stimulation and sensing may be used to determine thedegree of neurological block and/or neuromuscular block there between).Such functionality as well as directionality of the nerve signalpropagation (e.g. efferent, afferent, etc.) may be more easilydetermined through use of combined local stimulation and sensing.

Several patterns of nerve stimulation may be used to determine thefunction of the local nerve structures as well as any associated degreeof neurological block and/or neuromuscular block that may be caused bythe surgical procedure (e.g. ablation), anesthesia, abrasion, etc.

In aspects, a single stimulation pulse may be used to elicit maximalresponse from the associated nerve at frequencies of less than 10 Hz,less than 1 Hz, less than 0.1 Hz. The downstream response as measured byany of the described techniques will depend on the frequency with whichthe stimuli are applied. In order to allow for complete recovery of thenerve between stimulations, a frequency of less than or equal to 0.1 Hzmay be advantageous.

During RF ablation of an associated nervous structure, the evokedelectrical and/or muscular responses may be dramatically affected. Suchchanges in the response may be useful in determining the state of thedenervation procedure. Thus they may be advantageous to determine theexact degree of RF energy that must be applied to a given structure inorder to cause sufficient denervation as desired by a surgicalprocedure. Such an approach may be advantageous to limit damage tosurrounding tissues caused by the denervation procedure, to ensuresuitable denervation has been achieved, to determine which nerves areaffected by the procedure, etc.

Another technique for stimulation and sensing of the nervous responseincludes applying a rapid succession of pulses followed by a period ofinactivity. Pulse trains may be used to gradually force a nerve into ablocked state. The rate at which a nerve enters a blocked state andlater recovers therefrom may be a suitable indicator of the overallhealth and functionality of the nerve (i.e. as a suitable metric fordetermining how a procedure has affected that nerve).

Note that the sensing of the nervous response may not need to be localto a surgical site, but rather downstream (in the sense of the flow ofan associated nervous signal) from the site. In aspects, a guidewire inaccordance with the present disclosure may be configured to senseneurological activity caused by a stimulation event substantiallyupstream therefrom (i.e. the guidewire may be placed within theboundaries of the end organ).

Various mapping techniques may be applied to the surgical site, before,optionally during and after a surgical procedure. Some mappingtechniques as used in cardiac interventions include pace mapping,activation mapping, entrainment mapping, and substrate mapping. It maybe feasible to adapt at least some aspects of these techniques for usein the intended application. In general, these techniques may complementeach other in localizing where amongst a surgical site to target theablation procedure.

Additionally, or in combination to the aspects described herein, thesurgical system may be configured to monitor one or more physiologicparameters at one or more locations in the body remote from the surgicalsite. Some non-limiting examples of what may be monitored include waterconcentration, tone, blood oxygen saturation of local tissues, evokedpotential, local field potentials (LFP), stimulation/sensing of nervousactivity, electromyography, temperature, blood pressure, vasodilation,vessel wall stiffness, muscle sympathetic nerve activity (MSNA), centralsympathetic drive (e.g. bursts per minute, bursts per heartbeat, etc.),tissue tone, blood flow (e.g. through an artery, through a renalartery), a blood flow differential signal (e.g. a significantly abnormaland or sudden change in blood flow within a structure of the body, avessel, an organ, etc.), blood perfusion (e.g. to an organ, an eye,etc.), pupil dilation, electrolyte levels in a biofluid (e.g. anexudate, blood, urine, pancreatic fluid, bile salt, etc.), a bloodanalyte level (e.g. a hormone concentration, norepinephrine,catecholamine, renin, angiotensin II, an ion concentration, hemoglobinA1C, a water level, blood sugar levels, an oxygen level, etc.), nervetraffic (e.g. post ganglionic nerve traffic in the peroneal nerve,celiac ganglion, superior mesenteric ganglion, aorticorenal ganglion,renal ganglion, and/or related nervous system structures), combinationthereof, and the like.

A surgical system in accordance with the present disclosure may includeone or more elements to monitor physiologic activity and/or analytelevels (e.g. a hormone level), in and/or near to one or more portions ofa gland, an endocrine gland (e.g. an adrenal gland, an adrenal medulla,etc.), etc.

In aspects, a multi tool surgical system may be employed, each tool inaccordance with the present disclosure. In aspects, one or more firsttools may be used to probe and/or ablate tissues at a first surgicalsite (e.g. an artery, a renal artery, a left renal artery, etc.), whileone or more second tools may be configured to monitor one or morephysiologic parameters elsewhere in the body (e.g. in an alternativeartery, a vein, in an organ, at a lymph node, at a ganglion, etc.), todetermine the effect of the surgical procedure there upon, etc. Inaspects, the tools may be inserted into the same or closely positionedentry points into the body (e.g. a surgical port, an introducer, etc.).Such a configuration may be advantageous for providing a minimallyinvasive surgical tool to perform the surgical procedure (e.g. asympathectomy, a renal sympathectomy, a parasympathectomy, aneuromodulation, etc.) with monitoring performed at multiple, remotelocations within the body.

Some further aspects relating to systems and methods for adjusting(temporarily and/or permanently) nerve function, while substantiallyminimizing collateral damage to adjacent structures via endoscopic toolsand methods are now discussed. References made to ablation may beconsidered to refer to a general surgical procedure (to cut, heat, cool,excise, etc.) on a tissue.

In aspects, a tool in accordance with the present disclosure may includean array of electrodes and/or sensors. The array of electrodes and/orsensors may be arranged as to interface with one or more anatomicalsites within the body (e.g. along the walls of a lumen, walls of a renalartery, within an organ, a prostate, a pancreas, a liver, a kidney,etc.). The array of electrodes may be used to interfacecircumferentially and/or axially with the local tissues, so as to selectablation sites, validate ablation success, sense local neural activity,stimulate and sense, etc.

In aspects, one or more electrodes in the array may be used tostimulate, sense, and/or ablate local tissues and/or monitor nervousactivity before, during and/or after a related surgical procedure orablation process.

The tool may include a switch array in accordance with the presentdisclosure, optionally with one or more amplifiers such that one or moreelectrodes could be configured for stimulation, ablation, and/or sensingas part of a procedure. The tool may include electronics to monitorbioimpedance between one or more electrodes (e.g. so as to determinewhen the tool is adequately biased towards the intended anatomicalstructure, etc.).

The tool may include electronics for automatically terminating anablation signal when a change in the sensed nervous activity isdetected. In aspects, a pulsatile stimulation may be applied to one sideof the ablation zone, during the ablation process and/or betweenablation pulses (and/or intermixed with the ablation pulses). Anotherelectrode may be placed to the opposing side of the ablation zone so asto monitor nervous response before, during and/or after the ablationprocedure, during the pulsatile stimulation, or the like.

In aspects, individual electrodes in the array may be preconfigured soas to provide a particular signal conditioning function: sense,stimulate and/or ablate.

One or more electrodes in the array may be a monopolar electrode or partof a bipolar pair. In aspects, two or more electrodes may be arrangedinto pairs, multi-polar interconnects, etc.

In aspects, a tool in accordance with the present disclosure may includeone or more shielding elements placed in proximity to one or moreelectrodes in the array or to an interconnecting lead (e.g. a lead wire,an interconnection site, a switch, etc.). In the case of electrodes, thereadings from these electrodes may be used to balance and/or cancel outmacroscopic or environmental action potentials and/or noise from thelocal micro-electrode readings taking place at the clamp-tissueinterface. This approach may be used to lower the effective noise floorand improve the sensitivity of one or more of the micro-electrodes.

In aspects, one or more of the electrodes may be configured so as toprotrude from the surgical tool (e.g. via emboss, plating, filament,matted morphology, etc.). Any of the microelectrodes may be embossed soas to better bias the interfacing aspects towards the tissue during aprocedure. This may be advantageous to ensure that each electrodeapplies adequate pressure to the adjacent tissues and/or to improve thechances of tissue contact with a plurality of the electrodes

In aspects, a method for treating a surgical site with a surgical toolin accordance with the present disclosure includes locating the surgicalsite of interest; deploying the surgical tool near to the surgical siteor at a physiologically linked site within the body; monitoring electroactivity (e.g. neurological activity, MSNA, local field potentials,etc.) using one or more of the electrodes included in the surgical toolto determine a reference biosignal; applying a neurmodulation and/ordenervation signal (e.g. ablation, abrasion, current, light, etc.) tothe surgical site for a predetermined timeframe; monitoringelectrophysiological activity using one or more electrodes to determinean updated biosignal; and comparing at least a portion of the referencebiosignal or a metric derived therefrom with the reference biosignal ora metric derived therefrom in order to determine the extent of thedenervation.

In aspects, the method may include monitoring with different electrodesfor determining the reference and the updated signals, determining abioimpedance between electrodes during and/or after the neuromodulationprocedure, or the like.

In aspects, the method may include the application of multiple pulses,monitoring other physiologic signals, algorithmically combining suchsignals to generate the updated signal, extracting a metric from theneural activity and/or additional physiologic signals, confirming achange in the electrophysiological activity, combinations thereof, orthe like.

According to aspects there is provided, a method for determining theactivity levels of, directionality, location of and/or the extent ofnerve traffic and/or receptor functionality before, during and/or aftera surgical procedure may include stimulating a range of nerves locatedat a proximal and/or distal location on or within an organ (e.g. akidney, a renal artery, a gland, an adrenal gland, a ganglion, etc.) ina body; monitoring an evoked response at a location distal and/orproximal to the location of the stimulation; evaluating the signalquality, spectral content, etc. related to the evoked response and/orchanges in the evoked response during and/or after the surgicalprocedure.

In aspects, the method may include applying a stimulus to the body (e.g.an injection of a neuro-blocker, a neuro-stimulant, tilting the body, ashock, inducing a vascular spasm, etc.) and monitoring functionality,directionality, location of and/or the extent of nerve traffic and/orreceptor activity before, during and/or after the stimulus near one ormore nerves and/or at a site located on or within an organ (e.g. akidney, a gland, a ganglion, etc.), or a lumen (e.g. a renal artery, arenal vein, a ureter wall, etc.) in the body.

In aspects, one or more of the methods in accordance with the presentdisclosure may include electrically stimulating tissues at a stimulationlocation (e.g. one or more nerves, one or more receptors, etc.) with oneor more electrical pulses, thus forming a pulse train. A pulse train mayinclude a plurality of pulses with a predetermined spectral content(e.g. pulses centered around 10 Hz, 50 Hz, 100 Hz, 500 Hz, etc.) at oneor more locations proximal and/or distal to the surgical site.

In aspects, the pulse train may be applied locally to a neurologicalstructure, with an amplitude of generally 1.5×the voltage required toobtain a maximal amplitude compound action potential (CAP), with pulseduration of generally between 0.05 and 0.5 ms and interval of between 2ms (for 500 Hz spacing) to 10 s (for 100 mHz spacing). The overall pulsetrain may include one or more pulse types, evenly spaced withalternative timing over the application of the pulse train (so as toscan through a frequency range of interest). The corresponding nervousresponse may be monitored at another location on the vessel or in thebody. Such response may be monitored with a gain of generally 500 to 5 kand generally over a frequency band of 0.01 Hz to 10 kHz. Thisconfiguration may be used to evaluate the overall health and/orcapability of the nervous structure connecting the stimulating locationand the monitoring location.

In aspects, the local field potential may be monitored with pass bandcontent preserved at relatively low frequencies in order to determinethe near direct current (DC) changes in field potentials caused by thestimulus and/or surgical procedure. Such information may be reflectiveof changes in local analyte concentrations (i.e. as will affect thelocal Nernst potential formed by electrodes within the monitoring site),structural changes in the local anatomy (e.g. local tone, water content,low frequency movement, etc.), or the like. Such information may be asuitable surrogate for changes in sympathetic activity and/orneurological connection between the monitoring site and remote yetotherwise connected regions within the body.

During a surgical procedure, early indication of functional alterationto the nerve structure may be determined by monitoring for a change inthe properties of the sensed signal (e.g. a change in latency,amplitude, conduction velocity, spectral content, etc.). In onenon-limiting example, an ablation pulse may be applied to the nervebetween the stimulatory and monitoring locations. A change in theproperties of the sensed signal (e.g. a decrease in high frequencycontent therefrom, a change in latency, change in amplitude, etc.) maybe an early indicator that the ablation pulse is being applied properlyto the nervous structure situated there between. In addition, morepulses can be applied and the response monitored in order to observe thenerve response through to a sufficient state of functional alteration,such as desired as part of the neuromodulation procedure.

Monitoring may continue during a follow up period immediately after thesurgical procedure, and/or during a longer term period (e.g. hours,days, weeks, etc.). Such follow up may be used to determine the successof and/or prognosticate on the longevity of the surgical intervention.Such measurements may be advantageous in determining if a surgicalprocedure was properly applied in a seemingly non-responding patient.

In aspects, the technique may be used to identify the particular neuronsof interest to ensure that the correct neurons are being treatedsurgically (as well as to ensure that the extent of the treatment isacceptable). Such identification may involve monitoring a level ofneurological activity on the sensed nerve(s) to determine if the levelsare outside of a normal range (e.g. as compared with other sites in thebody, an activity metric for the patient population or a subset thereof,previously recorded measurements, etc.).

A method for generating a follow up schedule following a surgicalprocedure may involve monitoring the neurological activity of the sitewithin the body for a period of time (e.g. hours, days, weeks, etc.)after the surgical procedure; trending the neurological activity tocreate a metric relating to changes therein over the period of time; andpredicting recurrence data (e.g. probability of recurrence, a timeframeof recurrence, etc.) therefrom; and generating a follow up scheduledependent upon the recurrence data.

In aspects, a surgical tool and/or guidewire in accordance with thepresent disclosure may include a hook-like tip (with one or more sensorsor electrodes arranged thereupon) to make consistent and controlledcontact with the anatomy (so as to maintain a reliable contact with theintended monitoring site over a period of time). A soft hook-likestructure with tissue interfaces (electrode arrays, sensor arrays, etc.)fashioned towards the inner and/or outer surface of the hook may be usedto delicately contact the key anatomy during a surgical procedure (e.g.such as contact a region within the renal cortex of a kidney during aprocedure, to interface with a wall of a vessel, to interface with anadipose tissue, etc.). The hook may include a quick release (e.g. amechanical quick release, an electroactive material quick release, etc.)for simple removal from and/or positional correction in the vicinity ofthe monitoring site (e.g. around the cortex, within a vessel wall,within a tissue volume, etc.) during and/or at the conclusion of asurgical procedure.

In aspects, soft interfacing structures and/or hook-like structures maybe used to controllably interface with the tissues, applying contactpressures that are just suitable for sensing, stimulating, and/orablation procedures while minimizing the changes of unnecessary pressureinduced neural blockage during an associated procedure.

In aspects, a method for searching for a nerve of interest on the wallof a vascular vessel may include applying a point pressure on the wallof the vessel while monitoring distal and/or proximal nervous activity(e.g. monitoring, and/or stimulation and sensing on either side of thepoint pressure probe). Changes in the observed signals may be indicativeof pressure induced neural block due to the applied point pressure (i.e.thus identifying the location of the neural anatomy in question).

Relating to nerve compression syndrome, acute nerve compression studieshave shown some loss of nerve function through application of acutetransverse pressure above 40 mmHg, and loss of all nerve function atpressure application above 50 mmHg. Other studies have shown functionalblock under transverse compression when a pressure of 30 mmHg less thandiastolic pressure is applied and 45 mmHg less than the mean arterialblood pressure is applied to the nerve. Thus one or more components ofthe system (e.g. a clamp, an electrode element, a point pressureapplicator, etc.) may provide pressure variation above and/or belowthese ranges in order to assess nerve function, location, etc. asdescribed herein.

In aspects, a point pressure applicator in accordance with the presentdisclosure may be configured to operatively provide an oscillatingpressure to the test site, to synchronize pulsatile pressure applicationwith an array of probes, etc. so as to better orient a pair or array ofprobes for an ablation procedure.

In aspects, the holding force of one or more surgical elements (e.g. aclamp, a hook, a loop, a point pressure applicator, etc.) may becontrolled by various means including bioimpedance measurements,interfacial pressure sensors, micro-pulse oximetry based through flowand/or local perfusion measurements via optically equipped sensing tips,and the like. It may be desirable to control the application of forcefor various reasons such as causing signal inhibition via mechanicalcompression (nerve compression); for imposing a temporary nerve blockduring an associated procedure; to mask the underlying nervous activityduring surgical site selection; to control one or more contact pressuresand/or impedance for performing an associated ablation and/or monitoringprocedure.

In aspects, the surgical tool may include a means for applying a vacuumat sites in and around the electrodes. Such vacuum attachment may allowfor very intimate yet gentle contact between the adjacent tissue surfaceand the electrodes during a procedure.

In aspects, a soft flexible structure may be used in conjunction with asurface enhancement and/or wicking function (a hydrophilic material, aporous material, etc.) so as to draw fluid out from the vessel surfaceand use the resulting capillary forces and surface tension to form atight, intimate contact between the tool and the tissue suitable forneurovascular monitoring. This may be an option for long term placement(e.g. placing of an implantable component during a procedure for followup, etc.). Silk structures included into the flexible structure may besuitable for providing this functionality, optionally with a first layerthat can dissolve quickly and a second layer that may dissolve over thecourse of hours, days, weeks, etc.

In aspects, the flexible structure may include a medicament (e.g. aneural blocking agent, an anesthetic, lidocaine, epinephrine, a steroid,a corticosteroid, an opioid, alcohol, phenol, etc.).

In aspects, the structure may include a thin degradable supportstructure. In aspects, the support structure may quickly dissolve in thepresence of liquid (saline) such that it may be placed beside the vesseland wetted, so as to cause the remaining structure to change shape andbias against the vessel walls.

Such soft configurations may be useful to establish a reliable, yetgentle contact to a vessel surface or within an organ element,intimately contouring to the surface of the vessel or local anatomywithout applying excessive pressure thereto. Intimate yet soft contactmay be advantageous for reading sensitive neurological signals withoutinterfering mechanically with signal transmission thereof. Such softcontact may also be advantageous in reducing the relative movementbetween elements of the tool and the anatomy of interest.

A surgical tool in accordance with the present disclosure may includeone or more whiskers extending from a tool surface so as to reliablycontact an adjacent tissue structure during a surgical procedure. Thewhiskers may include electrodes, and the like.

Whisker penetration into an adjacent nerve bundle may be used to achievemore intimate contact thereto, as well as to better isolate electrodesfrom other macroscopic signal interference, etc.

Whiskers may be formed from microfibers, nanofibers, microneedles,nanoneedles, etc. In one aspect, one or more whiskers may be formed froma carbon structure, e.g. a carbon fiber, a carbon nanotube, etc. Thewhiskers may be insulated along a portion of their length, with anelectrically exposed region at the tip there upon.

In aspects, a boundary method for monitoring a surgical site during asurgical procedure may be employed. During this approach a plurality ofsensor tips may be arranged in contact around a perimeter of a surgicalregion on a tissue surface, whereby the electrophysiological signalsmeasured at locations along the surface may be used to determine thestate of the tissues within the boundary. For purposes of discussion,the boundary may be effectively the distal and proximal ends of thevessel or the extents of the surgical area, when applied to a tubularorgan of interest.

In aspects, a visual detection approach may be used in combination orcoordination with one or more surgical approaches in accordance with thepresent disclosure. Visual assessment may be used to at least partiallyguide the surgical procedure. The feedback may be in the form of avisible, a near infrared, infrared spectroscopic, or similar camerasystem, used in conjunction with the surgical tools, so as to bettervisualize the vessel/organ structure, identification of target anatomy(e.g. a nerve, nerve bundle, etc.) on the target organ (e.g. an artery,kidney, an adrenal gland, etc.), placement of tools onto the targetanatomy, etc.

In aspects, a backlit vessel lighting system may be used to assist withvisualizing the anatomy, locating target anatomy, etc.

In aspects, the system may include a feature enhancing medium, tohighlight targeted tissue species (e.g. highlight nerve tissues, etc.).The medium may include molecular binding species to selectively bindwith surface receptors on the intended target tissue, changing one ormore visual (chromatic) properties in the process and/or including avisual marking moiety. Some non-limiting examples of suitable molecularbinding species are peptides and aptamers. Suitable peptides andaptamers may be selected for target tissue (e.g. nerve tissue, fat,etc.) and may be selected as known in the art.

Inclusion of molecular binding species that have been selected for thetarget cells may be advantageous to assist with anatomical visualizationduring a surgical procedure. The molecular binding species may beprovided suspended in a delivery vehicle, such that it may beconveniently delivered to the target tissues during a procedure. Thedelivery vehicle may be a gel material, a 1 part curing gel, elastomer,etc. that may be conveniently delivered to the target tissues. A fullycurable vehicle may be advantageous for providing a simplified methodfor completely removing the medium from the body after the surgicalprocedure and/or targeting process has been completed.

Molecular binding species may include a visual marking moiety that isconfigured to improve visibility thereof. Thus the molecular bindingspecies will bind to the target tissue sites (e.g. nerve tissue, etc.),and will be highlighted by the visual marking moiety for visualizationwith an appropriate visualization system. Some non-limiting examples ofvisual marking moieties include: 5-carboxyfluorescein;fluorescein-5-isothiocyanate; 6-carboxyfluorescein;tetramethylrhodamine-6-isothiocyanate; 5-carboxytetramethylrhodamine;5-carboxy rhodol derivatives; tetramethyl and tetraethyl rhodamine;diphenyldimethyl and diphenyldiethyl rhodamine; dinaphthyl rhodamine;rhodamine 101 sulfonyl chloride; Cy3, Cy3B, Cy3.5, Cy5, Cy5.5, Cy 7,indocyanine green, IR800CW or combinations thereof.

This visualization approach may be advantageous to identify the keytissues for surgical procedures (e.g. neuromodulation procedures,sympathectomy, renal sympathectomy, etc.). By providing the material ina form suitable for surgical delivery and complete removal postoperatively, the resulting system may be safer compared to approachesthat require systemic application of the material.

A surgical system in accordance with the present disclosure may includeadditional functionality including: angiographic die delivery, salinedelivery, temperature monitoring, intra and extra vascular coordinationbetween devices, through wall imaging, through wall current flow, salineprovision for internal arterial cooling, and the like.

FIGS. 1a-d show aspects of a sensing guidewire 100 in accordance withthe present disclosure. The guidewire 100 is shown placed within anorgan 1 (such as a kidney) of a body. The guidewire 100 includes asensing tip 110 which is positioned within a region 3 (i.e. in this casethe renal cortex 3) of the organ 1. A volume 111 defined in the vicinityof the sensing tip 110 may be coupled with the sensing tip 110 during aprocedure (e.g. for purposes of monitoring, stimulating, treating,ablating, delivering a substance to, etc. tissues in the vicinity of thevolume 111). The guidewire 100 has been inserted endovascularly,percutaneously, etc. into a lumen in the body (e.g. a femoral artery, afemoral vein, a radial artery or vein, etc.) and directed to themonitoring site within the organ 1 shown. In the example shown, theguidewire 100 has been directed along the renal artery 5 (alternativelyalong a renal vein 7 or a ureter 9, via an aorta 11, a radial accesssite, a femoral access site, or the like, etc.) such that the tip 110 ofthe guidewire 100 is placed in intimate contact with one or moreelectroactive anatomical sites there within. In aspects, the guidewire100 may be placed such that the tip 110 is oriented within the lumen ofa vessel (e.g. an artery, a vein, a ureter, a renal artery, etc.) forobtaining physiologic information therefrom.

An alternative access point 125 is shown along the ureter 9, which wouldprovide access to the pelvic wall. In such a situation, the guidewire100 may be delivered such that one or more sensors located in the tip110 thereof may interface with the pelvic wall, thus monitoring one ormore activities associated with the sensory receptors (i.e. renalmechanosensory nerves) located therein.

In aspects, a guidewire 100 placed within the renal pelvis may bearranged so as to monitor electrophysiological activity during anassociated stimulus event, surgical procedure/event, follow upprocedure, stress test, etc. Such events may include a change in renalpelvic pressure (e.g. as induced by a change in posture, introduction ofbolus of fluid, altering blood pressure systemically, etc.),introduction of a vasodilator (e.g. bradykinin, etc.), locally to therenal pelvis, inducing a thermal change (e.g. changing a roomtemperature, introducing a hand into cold or warm water, cooling orwarming the blood, etc.), performance of a surgical procedure inaccordance with the present disclosure, combinations thereof, or thelike. The local electrophysiological response to such stimulus may be anindicator of the health of the kidney, may help to quantify the state ofthe sympathetic nervous system in the subject, may be used to determineor predict the extent that a subject may respond to a procedure, etc. Inaspects, the stimulus may cause a change in afferent signal activityfrom nerves innervating the renal pelvis, renal cortex, adrenal gland,etc. Such activity may be monitored at a second location near a neuralplexus along the renal artery or elsewhere in the body. The presence,change in, or absence of such signals at the second location may beindicative of the health of the neurological interconnection therebetween (e.g. the state of the nerves located between the two sites, theextent of a neuromodulation procedure, etc.).

The guidewire 100 may be connected to a controller 120 (not explicitlyshown) for purposes of capturing signals from the tip 110 thereof. Theguidewire tip 110 may include one or more sensors and/or electrodes,each in accordance with the present disclosure. The guidewire 100 mayinclude one or more electrical interconnects (not explicitly shown) atthe proximal end for interfacing with the controller 120.

Such a configuration may be advantageous for monitoring key physiologicinformation relating to a neuromodulation stimulus, a stress test, asurgical outcome, disease state, a surgical follow up, a neuroendocrinediagnostic, a neurological response to one or more of the above, etc. Inaspects, such information may be used for purposes of diagnosing adisease within a subject, for determining the outcome of a stimulus orsurgical procedure, for predicting the outlook of a subject after asurgery or a procedure, for predicting a subject's response to orsuitability for a neuromodulation therapy, etc.

FIG. 1b shows a schematic of a sensing guidewire 100 in accordance withthe present disclosure. The guidewire 100 includes a sensing tip 110 atthe distal end thereof. The sensing tip 110 may include one or moresensors and/or electrodes each in accordance with the presentdisclosure. The guidewire 110 may also include one or more connectors140 located at the proximal end thereof. The connectors 140 may bedimensioned and configured to interface with an interconnection module135 or a controller 120. Although shown separately, the interconnectionmodule 135 and the controller 120 may be integrated into a single unit.In aspects, a system in accordance with the present disclosure mayinclude both an interconnection module 135 and a controller 120 coupledtogether by a cable 145.

The guidewire 100 may include one or more leadwires and/or fibers toconnect elements in the sensory tip 110 to the connectors 140 thereof.In aspects, such leadwires may be constructed from one or more materialsknown in the art. In aspects, the leadwires and/or fibers may beconstructed from MRI compatible materials (e.g. resistive wires, carbonfibers, etc.) so as to minimize heating during use in MRI guidedsurgical procedures.

In aspects, the optional interconnection module 135 may include one ormore preamplifiers, multiplexers, switching networks, etc. each inaccordance with the present disclosure. Such a configuration may beadvantageous to minimize the length of leadwires between the sensing tip110 and the first signal amplification stage (i.e. a preamplifier in theinterconnection module 135).

In aspects, the guidewire 100 may include one or more microcircuits 130embedded therein. The microcircuits 130 may be coupled with one or moreelements within the sensing tip 110 as well as coupled to the connectors140. The microcircuits 130 may be dimensioned and configured to providesuitable preamplifier functionality, multiplexing operations, digitalcommunication hardware, etc. in order to improve signal integrity fromone or more elements within the sensing tip 110, to reduce lead wirecount, etc. In aspects, the microcircuits 130 may be coupled to elementsof the sensing tip 110 using an ultra-high density interconnecttechnology as known in the art and in accordance with the presentdisclosure.

In aspects, the microcircuit 130 may be implemented in an applicationspecific integrated circuit, as one or more bare die chipsets, flipchips, ultrafine pitch ball grid array mounted chipsets, chip scalepackages, ultra-fine blind via attachment, flexible HDI interconnects,wire bonded bare die, combinations thereof, or the like. In aspects, themicrocircuit 130 may be formed from a thinned silicon die, thinned to athickness of less than 100 μm, less than 50 μm, less than 10 μm, lessthan 5 μm. In aspects, the microcircuit 130 may be provided in anultralow profile flip-chip, chip scale package, with pitch scaling inthe range of 10-50 μm.

In aspects, an array of microcircuits 130 may be arranged upon asubstrate in accordance with the present disclosure to facilitateinterconnection with the sensing tip 110. The array of microcircuits 130may be arranged along the substrate and dimensioned so as to maintainthe small diameter aspects of the guidewire 100 (i.e. arranged in asingle file linear pattern along a predetermined length of the guidewire100). In aspects, the microcircuit 130 may be encapsulated in a polymerbead, inserted into a protective tube, inserted into the core of aguidewire spring shank, etc.

In aspects, the microcircuit 130 may be coupled with one or morestrengthening members so as to minimize the risk of damage to thecoupling between the microcircuit 130 and the sensing tip 110 or theconnectors 140. In aspects, the strengthening members may be configuredto as to allow for compression, tension, and/or torque transfer throughthe region of the guidewire 100 that includes the microcircuit 130.

In aspects, the controller 120 may include one or more user inputs (e.g.buttons, foot pedals, sliding mechanisms, touch screen displays, etc.)for providing the controller with user guided input so as to adjustsignal gain, deploy an aspect of a surgical tool, adjust a stimulationparameter, apply a stimulation, combinations thereof, or the like. Inaspects, the controller 120 may include a display for providing a userwith information relating to the physiologic signals, outcome of aprocedure, an electrophysiological map, combinations thereof, or thelike.

FIG. 1c shows aspects of methods for using a guidewire 100 in accordancewith the present disclosure. Although the methods describe accessing theparenchyma of an organ, they could be equally adapted to measuringelectrophysiological activity in vessels within a body (e.g. withinarteries, veins, a ureter, a urethra, etc.), for accessing a miniaturelumen within the body, etc. A first method 160 for diagnosing a medicalcondition is described that includes accessing the parenchyma of anorgan. By accessing the parenchyma of an organ is meant coupling asensor or electrode in accordance with the present disclosure with oneor more anatomical sites within the parenchyma of an organ, so as tomeasure one or more physiologic signals therefrom. The first method 160further includes recording physiologic activity from the parenchyma ofthe organ (e.g. with a sensor or electrode, a guidewire, a surgicaltool, etc. each in accordance with the present disclosure), andmonitoring a trend in the physiologic signal (e.g. during a stimulationevent, during a stress test, etc.), and/or making a diagnosis orprognosis based upon the recorded signal (e.g. a diagnosis of a diseasestate associated with local physiologic activity in the parenchyma ofthe organ, making a prognosis relating to an outcome of a disease stateassociated with activity in the parenchyma of the organ, etc.).

In aspects, the first method 160 may include one or more additionalsteps in accordance with the present disclosure. In aspects, the firstmethod 160 may include placing an additional tool including one or moresensors and/or electrodes at a remote location (with respect to theorgan) in the body and stimulating the local anatomy at either theremote site or within the parenchyma of the organ and monitoring anevoked response within the parenchyma of the organ or at the remote siterespectively. Such a configuration may be advantageous for elucidatinginformation about the connectivity between the two sites (i.e. relevantto determining if a neuromodulation procedure applied there between hasbeen successful, etc.).

A second method 170 is shown including accessing the parenchyma of anorgan in accordance with the present disclosure. The second method 170may further include recording physiologic activity from the parenchymaof the organ, performing a treatment on the body, recording a change inphysiologic activity, and determining if the treatment was successfullyapplied. In aspects, the second method 170 may include one or moreadditional steps in accordance with the present disclosure.

A third method 180 is shown including accessing the parenchyma of anorgan (alternatively an anatomical site of interest, a vessel, anartery, a vein, an arteriole, a venule, etc.), and mapping theelectrophysiological activity in the vicinity of the anatomical site ofinterest. The mapping may be provided by sweeping a sensory tip inaccordance with the present disclosure over the anatomical site ofinterest, inserting and then withdrawing the sensory tip, deploying thesensory tip and then dragging and/or rotating the deployed tipalong/around the lumen wall, combinations thereof, and the like. Inaspects, the third method 180 may include displaying the mappedphysiologic information for a user, constructing an anatomical modeltherefrom, directing a surgical robot to perform a treatment therefrom,comparing the map with a previously determined map (e.g. as a means formonitoring the outcome of a procedure, tracking a therapy, etc.),combinations thereof, or the like. In aspects, the method may includeproviding one or more directions to a surgeon and/or a surgical robot toaccess one or more regions of the mapped anatomy, overlaying the presentmap with previously generated maps (so as to evaluate changes infunctionality, activity, etc.), combinations thereof, and the like.

A fourth method 190 is described including accessing an anatomical siteof interest within the parenchyma of an organ, stimulating one or morephysiologic systems in the body, and monitoring the evoked response atthe anatomical site of interest. The fourth method 190 may includeassessing the functionality of the anatomical site of interest, the siteof stimulation (i.e. if the stimulation is of a localized type), or ananatomical site there between.

In aspects, the method may include ablating one or more anatomical siteswithin the body.

In aspects, one or more methods in accordance with the presentdisclosure may be completed, at least in part, with a guidewire 100 inaccordance with the present disclosure.

FIG. 1d shows a schematic of a sensing guidewire 102 in accordance withthe present disclosure. The guidewire 102 may include one or more zonessuch as a sensing tip 112, a sensing/ablation/stimulation zone 114,and/or a second sensing zone 132 each located towards the distal endthereof. One or more of the zones may include aspects for sensing,ablating, stimulating, biasing against adjacent tissues, etc. Inaspects, the sensing tip 112 may include one or more sensors and/orelectrodes each in accordance with the present disclosure. In aspects, asecond zone 114 may be configured to bias 137 one or more aspects of theguidewire 102 against an adjacent lumen wall for purposes of couplingthereto (such as to perform a procedure in accordance with the presentdisclosure, etc.). In aspects, a third zone 132 is shown, configured soas to interface with an adjacent lumen wall for purposes of sensing,ablation, stimulation, combinations thereof, or the like.

In aspects, the guidewire 102 may also include one or more connectors142 in accordance with the present disclosure located at the proximalend thereof. The connectors 142 may be dimensioned and configured tointerface with an interconnection module 138 or a controller 122.Although shown separately, the interconnection module 138 and thecontroller 122 may be integrated into a single unit. In aspects, asystem in accordance with the present disclosure may include both aninterconnection module 138 and a controller 122 coupled together by acable 147.

In aspects, the optional interconnection module 138 may include one ormore preamplifiers, multiplexers, switching networks, etc. each inaccordance with the present disclosure. Such a configuration may beadvantageous to minimize the length of leadwires between the sensing tip112 and the first signal amplification stage (i.e. a preamplifier in theinterconnection module 138).

In aspects, the guidewire 102 may include one or more microcircuitsembedded therein (herein embedded within one or more of the zones 112,114, 132). The microcircuits may be coupled with one or more elementswithin the sensing tip zone 112 as well as coupled to the connectors142. The microcircuits may be dimensioned and configured to providesuitable preamplifier functionality, multiplexing operations, digitalcommunication hardware, etc. in order to improve signal integrity fromone or more elements within the sensing tip zone 112, to reduce leadwire count, etc. In aspects, the microcircuits may be coupled toelements of the sensing tip zone 112 using an ultra-high densityinterconnect technology as known in the art and/or in accordance withthe present disclosure.

In aspects, one or more of the zones 112, 114, 132 may be configured soas to interface with an adjacent anatomical feature along which atreatment is desired. Information and/or treatment provided by each zonemay be used to determine effective delivery of treatment to a regionalong the anatomical feature (i.e. physiologic sensing and/orstimulation provided at sites within zones 112, and 132 may be used todetermine the effectiveness of a neuromodulation therapy provided to theadjacent tissues in the vicinity of zone 114). In aspects, atherapeutic, stimulatory, and/or sensing configuration may be coupledbetween zones 112, 114, 132.

In aspects, one or more steps of a method in accordance with the presentdisclosure may be performed with one or more zones 112, 114, 132 of aguidewire 102 in accordance with the present disclosure.

The connectors 142 may be dimensioned and configured to interface withan interconnection module 138 or a controller 122. Although shownseparately, the interconnection module 138 and the controller 122 may beintegrated into a single unit. In aspects, a system in accordance withthe present disclosure may include both an interconnection module 138and a controller 122 coupled together by a cable 147.

In aspects, the optional interconnection module 138 may include one ormore preamplifiers, multiplexers, switching networks, etc. each inaccordance with the present disclosure. Such a configuration may beadvantageous to minimize the length of leadwires between the sensing tip112 and the first signal amplification stage (i.e. a preamplifier in theinterconnection module 138).

FIGS. 2a-p show aspects of sensing tips 110, and/or zones 112, 114, 132associated with a sensing guidewire 100, 102 in accordance with thepresent disclosure. FIG. 2a shows a sensing guidewire 201 including oneor more sensors or electrodes 202 located at the distal tip thereof. Inaspects, the electrodes 202 may be arranged in patterns around thecircumference of the tip so as to contact a lumen wall if the guidewire201 is introduced deep enough into the lumen so as to bottom out (i.e.as the lumen diameter shrinks distally heading into the organ). Theelectrodes 202 may be connected to a controller 205, a preamp, amicrocircuit, a connector, or the like in accordance with the presentdisclosure. Such interconnection may be provided by one or moreleadwires 204 arranged along the length of the guidewire 201. Inaspects, one or more of the leadwires 204 may be integrated into thewalls or jacket of the guidewire 201. In such configurations, theleadwires 204 may be helically integrated, and/or braided into the wallsor jacket, or equivalently threaded, coextruded, plated, shrink wrapped,or pultruded within the walls of the guidewire 201 (i.e. or equivalentlythreaded through one or more microlumen within the wall of the guidewire201).

The electrodes 202 may be formed in accordance with the presentdisclosure. In aspects, the electrodes 202 may be formed directly fromthe tips of the one or more leadwires 204. The tips of the leadwires 204may be formed into microelectrode elements, with predetermined exposedareas and tip profiles, suitable for monitoring electrophysiologicalactivity at the site of interest. In aspects, the predetermined exposedareas may be designed so as to lean towards single unit recordings (e.g.electrode area less than 250 μm², less than 150 μm², less than 100 μm²),multi-unit recordings (e.g. electrode area of greater than 500 μm²,greater than 1000 μm², greater than 2000 μm²), and large area orreference field recordings (e.g. electrode area greater than 10,000 μm²,or the like). In aspects, the electrodes 202 may be treated so as toalter the impedance thereof, during use. In aspects, the electrodes maybe processed so as to increase the capacity thereof such as viaconversion to, plating of, or augmentation with an electric energystorage (EES) material, an intercalating material, surface areaincreasing process, a plating process, combinations thereof, or thelike. In aspects, each electrode 202 may be configured with a profilesuited for accessing the anatomy of interest (e.g. a needle-likestructure, an embossed structure, a whisker like structure, a dendriticstructure, etc.).

FIG. 2b illustrates aspects of a sensing tip of a guidewire 206 with adeployable tip array 208 arranged near to or at the distal tip thereof.Optionally, the guidewire 206 may include a jacket 207 arranged alongthe length thereof. The jacket 207 may be configured so as to slidealong a core structure, the core structure supporting the deployable tiparray 208. Thus, retraction of the jacket (or equivalently protrusion ofthe core structure) may be used to deploy the elements of the deployabletip array 208 once the tip of the guidewire 206 has been delivered to ananatomical site of interest. The deployable tip array 208 may includeone or more microfingers 210 in accordance with the present disclosure.Each microfinger 210 may include one or more sensors or electrodes inaccordance with the present disclosure. In FIG. 2b , a guidewire 206 isshown with an array of microfingers 210, each equipped with amicroelectrode 209 upon the distal tip thereof. The microelectrodes 209and microfingers 210 may be configured so as to bias towards a lumenwall upon deployment, or configured so as to penetrate the lumen wallupon deployment or during a penetrating maneuver (e.g. pushing thedeployed tip array 208 forward along the lumen wall, etc.). In aspects,the microfingers 210 may be actuated so as to facilitate deployment(e.g. via an electroactive, electrochemical, mechanical, and/orthermomechanical activation means). In aspects, the microfingers 210 maybe one-time deployable via a biodegradable mechanism (e.g. dissolutionof an adhesive binding element, a thermally activated material, etc.).

In aspects, one or more of the microfingers 210 may be shaped such thatit forms the desired shape upon deployment (subject to the dimensions ofthe local anatomy). In aspects, the microfingers 210 may be configuredto form an umbrella like structure, a basket like structure, a helicalstructure, a star like structure, a porcupine like structure, etc.

One or more elements of the sensing tip may be interconnected with acontroller 211, preamp, microcircuit, circuit, a connector, or the likein accordance with the present disclosure.

FIG. 2c shows aspects of a sensing tip of a guidewire 215 in accordancewith the present disclosure. The sensing tip includes a j-curved segment216 which may be configured with a subminiature bend radius. In aspects,the j-curved segment 216 may be formed with a radius of less than 4 mm,less than 3 mm, less than 1 mm. The sensing tip may include one or moreelectrodes 217, 218. As shown in FIG. 2c , the sensing tip may includeone or more microelectrodes 217 and one or more reference electrodes 218(optional). The microelectrode 217 may be exposed to the surroundingsover a subset of the overall tip area (e.g. over an area most likely tobias against a lumen wall during insertion, over a region facing awayfrom the axis of the j-curve segment 216, etc.). In aspects, thereference electrode 218 may be formed by exposing and/or processing asegment of the guidewire 215 (e.g. removing an insulating coatingtherefrom, plating a material thereto, swaging a tube onto the guidewiresegment, etc.). The electrodes 217, 218 may be coupled to a connectorand/or a controller 220, preamp, microcircuit, circuit, a connector, orthe like in accordance with the present disclosure.

The j-curved segment 216 may be advantageous to maintain contact withthe walls of a lumen during a placement procedure. In aspects, thej-curved segment 216 may be dimensioned with a predetermined radius andconfigured with a predetermined stiffness such that the electrodes 217,218 may consistently contact the walls of vessels with a characteristicdiameter within a predetermined range (e.g. 2-8 mm, 1-4 mm, 0.5-2 mm,etc.). The j-curved segment 216 may also be configured so as to bias 219the electrodes against the wall of a lumen during a study.

In aspects, the j-curved segment 216 may include one or more strainmeasuring elements (e.g. a strain gauge, a piezoresistive material,etc.) configured to measure the diameter of the lumen into which theguidewire 215 has been placed.

FIG. 2d illustrates aspects of a sensing tip of a sensing guidewire 221in accordance with the present disclosure. The guidewire 221 includes apushable core 222 or equivalently a retractable sheath 223 configured sothat the core can be deployed once the guidewire 221 has been directedto an anatomical site of interest. In aspects, one or more of the tipconfigurations disclosed herein may be attached to the pushable core 222in order to construct a sensing guidewire 221 with a deployable 222 atip structure (e.g. with a deployable tip array, a basket arrangement,etc.). The pushable core 222 is also illustrated in a deployed position224 to illustrate interfacing one or more electrodes there upon with anearby anatomical site.

In aspects, the core 222 may be coupled with a controller 225, preamp,microcircuit, circuit, a connector, or the like each in accordance withthe present disclosure.

FIG. 2e shows aspects of a sensing tip of a guidewire 226 in accordancewith the present disclosure. The guidewire 226 includes a microbasketelectrode array 227 including an array of micofingers 229, each arrangedin a bowed shape so as to extend out from the axis of the lumen intowhich the device is placed. Aspects of a single microfinger 229 in thearray is shown in the detailed view A. The microfinger 229 includes oneor more sensors or electrodes 228, each in accordance with the presentdisclosure. In the example shown in FIG. 2e , the electrode 228 is shownpatterned so as to face radially outwards from the center of the lumeninto which the sensing tip is deployed. The electrode 228 may be formedin accordance with the present disclosure. One or more regions of themicrofinger 229 may be isolated from the surroundings with an insulatinglayer (e.g. a passivated layer, a dielectric layer, a polymer, PTFE,parylene, etc.). In aspects, the microfinger 229 may be configured so asto deploy to reach the shape shown in FIG. 2e during a predeterminedprocedure (e.g. actuation, sheath retraction, core extension,biodegradation of a restraint, etc.). In aspects, the microbasket array227 may be deployed during use so as to interface with the walls of alumen, in accordance with the present disclosure. One or moremicrofingers 229 and/or sensors or electrodes 228 may be coupled with aconnector or a controller 230, preamp, microcircuit, circuit, aconnector, or the like each in accordance with the present disclosure.

FIG. 2f illustrates aspects of a sensing tip of a sensing guidewire 231in accordance with the present disclosure. The guidewire generallyincludes one or more lumens and a microporous tip 232 which includes oneor more ports 238 through which one or more protruding microneedleelements 234 may pass upon deployment. The guidewire 231 is shown in aretracted state 236 which may be suitable for accessing a targetanatomical site in accordance with the present disclosure, as well as ina deployed state 237 which is suitable for interfacing one or moresensors or electrodes with the target anatomical site as part of aprocedure. One or more of the protruding microneedle elements 234 mayinclude a sensor or an electrode on the exposed tip 233 thereof. One ormore of the microneedle elements 234 may include one or more features235 such as bumps, step changes in insulation, etc. configured so as tolimit the penetration depth of such exposed tips 233 into the adjacenttissues. One or more aspects of the guidewire 231 or aspects of theexposed tips 233 may be coupled to a controller 239, preamp,microcircuit, circuit, a connector, or the like each in accordance withthe present disclosure.

FIG. 2g shows aspects of a sensing tip of a sensing guidewire 241 inaccordance with the present disclosure. The sensing guidewire 241includes a plurality of deployable tines 242, each tine 242 includingone or more sensors and/or electrodes each in accordance with thepresent disclosure. The deployable tines 242 may be held together duringstorage and delivery to a surgical site of interest by a restraintmechanism 243 (such as a biodegradable adhesive, a water soluble matrix,a thermally stabilized shape set, etc.). Upon delivery to the anatomicalsite, upon contact with a fluid, etc. the restraint mechanism 243 mayrelease the tines 242 so as to deploy 244 them to form a deployed state.In the deployed state, the tines 242 may be significantly biased 247towards the walls of a lumen into which the sensing tip has been placed,etc. One or more aspects of the guidewire 241 or aspects of the tines242 may be coupled to a controller 246, preamp, microcircuit, circuit, aconnector, or the like each in accordance with the present disclosure.

FIG. 2h shows aspects of a sensing tip of a sensing guidewire 251 inaccordance with the present disclosure. The sensing tip includes one ormore microfingers 252 in accordance with the present disclosure. Themicrofingers 252 shown in FIG. 2h are equipped with a plurality ofsensing points 253, each including a sensor or electrode in accordancewith the present disclosure. The sensing guidewire 251 is shown placedwithin a lumen 25 within a body and the microfingers 252 have beendeployed such that the sensing points 253 may interface with the wallsof the lumen 25. One or more of the sensing points 253 may be coupledwith a controller 254, preamp, microcircuit, circuit, a connector, orthe like each in accordance with the present disclosure in order torecord signals therefrom during a monitoring session. In aspects, thesensing guidewire 251 may be retracted while in the position shown so asto drag 255 the sensing points 253 along the walls of the lumen 25, soas to map the physiologic signals there upon. In aspects, such aconfiguration may be advantageous for mapping electrophysiologicalinformation along the lumen wall, for generating an anatomical map, forevaluating the location of active neuromuscular sites, evaluating thetype and/or direction of neurological traffic in the vicinity of eachsensing point 253, etc.

FIG. 2i illustrates aspects of a sensing tip of a sensing guidewire 260in accordance with the present disclosure. The sensing tip includes ajacket 262 and a shaped tip 264, the jacket 262 dimensioned with adiameter 270 sufficiently small so as to access an anatomical site ofinterest within a body. The sensing tip further includes one or moresensors 266 each nested into an access port. The guidewire 260 alsoincludes one or more lead wires 268 interconnected with the sensors 266and the proximal end of the guidewire 260 (e.g. a connector, amicrocircuit, a controller 272, a preamp, microcircuit, circuit, aconnector, etc.).

In aspects, one or more of the sensors may be configured to monitor alocal analyte concentration (e.g. a hormone concentration,norepinephrine, catecholamine, renin, angiotensin II, an ionconcentration, a water level, an oxygen level, etc.), a pH level, etc.

FIG. 2j illustrates aspects of a delivery catheter 269 in accordancewith the present disclosure. The delivery catheter 269 may provide asheath through which one or more additional elements may be guided 272to an anatomical site within the body and/or to interconnect a distalportion thereof with a controller 270, preamp, microcircuit, circuit, aconnector, or the like. The delivery catheter 269 may include one ormore electrodes 271 configured for purposes of sensing, stimulation,stress test analysis, neuromodulation, surgical procedural outcome,changes in traffic associated therewith, as reference electrodes, or thelike. In aspects, the delivery catheter 269 may include a bulbousfeature 273 sized and dimensioned so as to provide a stop gap forentrance into a target lumen, for providing hemostasis within a targetlumen, etc.

FIG. 2k illustrates aspects of a delivery catheter 275 with a hollowlumen configured along the length thereof, including one or more sensors277, a bulbous feature 278 each in accordance with the presentdisclosure. The delivery catheter 275 is shown with an associatedguidewire 279, deployed from the tip thereof. The guidewire 279 includesone or more zones 280, 281, 282 each in accordance with the presentdisclosure. The guidewire 279 includes a sensing tip 280 attached to asoft guiding tip 281 configured so as to measure one or more physiologicaspects of an adjacent tissue when positioned within a lumen of a body.The guidewire 279 includes a biasing zone 282 including one or moreelectrodes and/or sensors, each in accordance with the presentdisclosure. In aspects, the biasing zone 282 may be configured to deployupon protrusion of the guidewire 279 tip beyond the delivery catheter275, upon retraction of the delivery catheter 275, upon actuation of anelement within the biasing zone 282, upon adjustment of a repositionablecore within the guidewire 279, or the like. The guidewire 279 may beconfigured so as to advance 283 or retreat 284 along the length of alumen into which it is placed during a procedure.

In aspects, the guidewire 279 may include a repositionable core in orderto construct a sensing guidewire 279 with a deployable tip structure(e.g. with a deployable tip array, a basket arrangement, helical biasingzone 282, etc.).

In aspects, one or more sensors and/or electrodes (i.e. included within282, 280) on the guidewire 279 may be configured to communicate with oneor more sensors and/or electrodes 277 on the delivery catheter 275.

FIG. 2l illustrates aspects of a guidewire 2201 in accordance with thepresent disclosure coupled with a lumen wall 25 into which it has beendeployed (i.e. as part of a procedure). The guidewire 2201 may becoupled with a controller 2203 in accordance with the presentdisclosure. The guidewire 2201 may include one or more sensing tips 2205for interfacing with the lumen wall 25. The guidewire 2201 may include asoft tip 2207 for assisting with delivery of the guidewire 2201 into thelumen. In aspects, the guidewire 2201 may include one or more electrodes2209 positioned near to the distal tip of the guidewire 2201 within abiasing zone 2211 in accordance with the present disclosure. The biasingzone 2211 includes a helically shaped region (i.e. such as formed in ashape setting procedure, etc.), so as to bias the electrodes 2209against the lumen wall 25 upon deployment.

In aspects, the guidewire 2201 may be configured with a characteristicdiameter d, of less than 1.5 mm, less than 1 mm, less than 0.75 mm, lessthan 0.5 mm, less than 0.25 mm, or the like. The shape set aspects ofthe biased zone 2211 may be configured so as to transition from adisconnected region along the lumen wall 25 into a zone of contact, soas to provide consistent contact with the lumen wall 25 during aprocedure. In aspects, the guidewire 2201 may be configured so as totransition from a substantially elongate shape to a deployed shape (e.g.a helical electrode arrangement, etc.), upon deployment into the lumenof a vessel within a body.

In aspects, the guidewire 2201 may be configured for placement within avessel, for delivery to or within the parenchyma of an organ into whichthe vessel extends, or the like as part of a surgical procedure. Inaspects, the guidewire 2201 may be configured for nerve monitoring,electrophysiological monitoring, stimulation, and/or ablation proceduresin accordance with the present disclosure.

In aspects, the guidewire 2201 may be configured to provide a path, overwhich a second surgical tool may be delivered to the vessel, theguidewire sensing tip 2205 configured to monitor one or more physiologicfunctions relevant to the operation and/or evaluation of a procedureperformed by the surgical tool.

In aspects, one or more of the zones 2205, 2211, etc. may be configuredfor sensing local electrophysiological activity, stimulating localneural anatomy, delivering a substance to local tissues, and/orneuromodulating local neural anatomy (e.g. ablating, denervating, etc.)in accordance with the present disclosure. In aspects, a guidewire inaccordance with the present disclosure may include a sensing zone 2205located at the distal tip thereof, an ablating/stimulating zone 2211located along the length of the guidewire proximally to the distal tip,and a second sensing zone 132 shown in FIG. 1d located along the lengthof the guidewire proximally to the ablating/stimulating zone. Inaspects, functions performed within each zone 112, 114, and 132 shown inFIG. 1d , 2201 and 2211 shown in FIG. 2l , etc. during a procedure maybe coordinated by a controller in accordance with the present disclosurefor purposes of diagnosis, determining the extent of a procedure,performing a neuromodulation procedure, denervating a neural structure,combinations thereof, or the like.

In aspects, the guidewire 2201 may be configured with a shape set region2211, configured to bias 2213 one or more regions 2211 of the guidewireagainst a wall of a lumen 25 into which it has been placed. In aspects,the guidewire 2201 may include a wire basket, a helical region, aballoon, etc. in order to provide such bias 2213 against an adjacentlumen wall 25. In aspects, the shape set region 2211 may be retractablycollapsible into a delivery sheath (i.e. a sheath provided over theguidewire sized and dimensioned for delivery thereof to an anatomicalsite of interest). In aspects, the shape set region 2211 may be deployedso as to bias against a wall of a lumen 25 into which it is placed by anactuation procedure, retraction of a delivery sheath, protrusion of theguidewire distal tip beyond the distal tip of a delivery sheath, etc.

In aspects, the biasing region 2213 may be deployed via actuation of anactuator element embedded therein. In aspects, such an actuator elementmay include an active material transducer in accordance with the presentdisclosure. In aspects, the actuation may be provided by a shape setshape memory alloy, such as may be introduced into the lumen at atemperature substantially below a threshold transition temperature, andundergo a deployment so as to bias against the lumen wall 25 uponincreasing temperature to substantially above the threshold transitiontemperature (e.g. such as via natural heating from adjacent tissuestructures, via active heating, via current flow associated with astimulation and/or ablation procedure, etc.). In aspects, suchdeployment may be achieved by other forms of actuation such as but notlimited to electroactive material expansion, retraction of a centralcore, pulling of a tendon core, retraction of a sheath, dissolution of aconstraining element, etc.

In aspects, a guidewire in accordance with the present disclosure mayinclude a bulbous feature located within the vicinity of the distal tipthereof. The bulbous feature may be configured to bottom out theguidewire within a lumen (e.g. when the lumen diameter approaches thatof the bulbous feature, between a step between a feeding lumen and atreatment lumen, etc.) as it is advanced there along during a placementprocedure. Such a feature may be advantageous to position the distal tipof the guidewire within a treatment lumen (e.g. a vessel, an artery, avein, a tubule, etc.), to provide hemostasis to the treatment lumen,etc.

FIG. 2m illustrates aspects of a guidewire 2215 in accordance with thepresent disclosure. The guidewire 2215 may be coupled with a controller2225 in accordance with the present disclosure. The guidewire 2215 mayinclude one or more sensing tips 2217 for interfacing with a localanatomical site during a procedure. The guidewire 2215 may include asoft tip 2217 for assisting with delivery of the guidewire 2215 into alumen within a body. In aspects, the guidewire 2215 may include one ormore electrodes 2219 positioned near to the distal tip of the guidewire2215 within a biasing zone 2218 in accordance with the presentdisclosure. The biasing zone 2218 shown in FIG. 2m includes a helicallyshaped region (e.g. such as formed in a shape setting procedure, etc.),so as to bias the electrodes 2219 against an adjacent wall during aprocedure. In the biasing zone 2218 may take a deployed form 2220 duringplacement, or as part of a placement procedure. In aspects, the deployedform 2220 may take on a bulbous shape, an expanded region with taperedends, a cylindrical profile, or the like.

In aspects, the biasing zone 2218 may include a shape set aspect,configured so as to transition from a first shape that is notsufficiently biased so as to contact an adjacent lumen wall, to a regionover which the biasing is sufficient to provide consistent contact withan adjacent lumen wall during a procedure. In aspects, the biasing zone2218 of the guidewire 2215 may be configured so as to transition from asubstantially elongate shape to a deployed shape (e.g. a helicalelectrode arrangement, etc.), upon deployment into the lumen of a vesselwithin a body.

In aspects, the guidewire 2215 may be configured with one or morediameters along the length thereof. In aspects, a distal characteristicdiameter d₁, for the guidewire 2215 may be arranged such that d₁ is lessthan 1.5 mm, less than 1 mm, less than 0.75 mm, less than 0.5 mm, lessthan 0.25 mm, or the like. In aspects, a proximal characteristicdiameter d₂ may be arranged such that d2 is less than 1.0 mm, less than0.75 mm, less than 0.5 mm, less than 0.025 mm, or the like. In aspects,the proximal diameter d₂ may be sized so as to provide a sufficientlyminiature profile over which an additional catheter and/or surgical toolmay be deployed within the body. In aspects, the distal characteristicdiameter d₂ may be configured so as to accommodate an embeddedmicrocircuit 2223 and/or interconnections thereto.

In aspects, a guidewire 2215 in accordance with the present disclosuremay include a microelectronic circuit 2223 embedded within or coupled tothe distal tip 2217 thereof, as well as coupled to an interconnectand/or controller 2225 coupled to the proximal end thereof, configuredto control signal flow to/from one or more zones 2218, 2217, etc. of theguidewire 2215 for purposes of performing a procedure in accordance withthe present disclosure.

In aspects, a guidewire in accordance with the present disclosure mayinclude one or more electrodes, each electrode configured to sense,stimulate, and/or ablate a local anatomical site within a body. Inaspects, the guidewire may include a plurality of ablation electrodesconfigured to interface with a wall of a lumen into which the guidewireis placed, so as to provide coupling for delivery of radiofrequency,and/or microwave frequency energy into the wall of the lumen and/ortissues surrounding the lumen, as part of a procedure in accordance withthe present disclosure. In aspects, the guidewire may be configured tomonitor one or more physiologic aspects in conjunction with the energydelivery process (e.g. before, during, after, etc.).

In aspects, a system in accordance with the present disclosure mayinclude a delivery catheter including one or more electrodes, and aguidewire including one or more electrodes, the system configured topass energy between the catheter electrode(s) and the guidewireelectrode(s) as part of a procedure. In aspects, the system may beconfigured to monitor electrophysiological activity between theguidewire electrode(s) and the catheter electrode(s) as part of aprocedure.

In aspects, a guidewire in accordance with the present disclosure mayinclude a drug eluting region (e.g. over an electrode, at the distaltip, etc.), configured so as to elute a drug into the vicinity of theregion during a procedure (e.g. so as to minimize clotting, minimizedamage to adjacent structures, etc.).

In aspects, a guidewire in accordance with the present disclosure mayinclude a thrombus net coupled to the distal tip thereof. The thrombusnet may be configured so as to bridge a cross section of a lumen intowhich the guidewire is placed during a procedure. The thrombus net maybe configured to capture debris generated at a site along the system,guidewire, associated catheter, etc. during a procedure in accordancewith the present disclosure. The thrombus net may be configured so as towithdraw any captured debris along with the guidewire during withdrawalfrom the body.

FIG. 2n illustrates aspects of placement of a delivery catheter 2230 anda guidewire 2240 each in accordance with the present disclosure placedwithin a body. The delivery catheter 2230 may include a bulbous feature2236 to assist with placement thereof within a feeder lumen 30 and/or atreatment lumen 35 within the body. The delivery catheter 2230 mayinclude a hollow core to facilitate delivery of an associated guidewire2240 into the treatment lumen 35. In aspects, the guidewire 2240 mayinclude a plurality of zones, such as a biasing zone 2242 forinterfacing one or more electrodes/sensors, and/or a sensing tip zone2244 with a wall of the target lumen 35. The delivery catheter 2230and/or the guidewire 2240 may be interconnected with a controller 2232in accordance with the present disclosure. In aspects, the deliverycatheter 2230 may include one or more sensing, stimulation, and/orablation zones 2234, 2238 in accordance with the present disclosure. Inaspects, such a zone 2238 may be coupled to a bulbous feature 2236.

FIG. 2o shows non-limiting examples of aspects of a feeder lumen 37 a,b,a main lumen 39 a-d, and a variety of additional lumens 41 a-d, whichmay be considered in the treatment of a disease state, analysis oftraffic thereby during a stress test, a diagnostic procedure, atreatment, or the like. Such lumens may be accessed via one or moreapproaches 49 a-c (e.g. via one or more access points into the body, avascular access point, a venous access point, an arterial access point,etc.). In aspects, the main lumen 39 a-d may be interconnected with oneor more additional lumens 41 a, d. In aspects, the feeder lumen 37 a,bmay be interconnected with one or more additional lumens 41 b, c.

In aspects, one or more additional lumens 41 b,c may not be easilyaccessed via the main lumen 39 a-d. As such, an alternative approach(e.g. via an interconnected lumen, etc.), may be used to deliver adevice in accordance with the present disclosure to the additionallumens 41 b,c.

In aspects, a system, device, or method in accordance with the presentdisclosure may be used to treat a plurality of organs 1 a,b, 2 a,b (e.g.a kidney 1 a,b, a adrenal gland 2 a,b). A method in accordance with thepresent disclosure may include inserting at least a portion of a systemor guidewire in accordance with the present disclosure into a main lumen39 a-d, or one or more additional lumens 41 a-d and treating one or moreregions there within. The method may include monitoring one or morephysiologic signals, local electrophysiological signals, etc. to assesscompletion of the treatment, and/or to determine if further treatmentsites are necessary to complete the intended procedure (such as acomplete sympathectomy, controlled sympathectomy, etc.). In aspects, amethod in accordance with the present disclosure may include withdrawinga portion of a system or guidewire in accordance with the presentdisclosure from a first lumen 39 a-d, 41 a-d, and delivering it into analternative lumen and continuing with a procedure in accordance with thepresent disclosure.

In aspects, a method in accordance with the present disclosure mayinclude treating one or more regions within or within the vicinity ofone or more additional lumens 41 a-d so as to ensure treatment has beencompleted.

In aspects, a method for treating hypertension is provided includingtreating neurological tissues running in the vicinity of a main lumen 39a-d and additional lumen 41 a-d so as to substantially denervate allsympathetic and/or parasympathetic nerves coupled with the organ 1 a,b,2 a,b. In aspects, the method may include treating the nerves coupledwith the adrenal glands 2 a,b.

In aspects, a method in accordance with the present disclosure mayinclude locating one or more additional lumens 41 a-d. In aspects, suchlocating may be performed with an imaging system (e.g. with a computedtomography system, HRCT, MRI, fMRI, positron emission tomography,ultrasound, OCT, combinations thereof, or the like) to produce one ormore images (e.g. 2D images, 3D images, etc.) thereof and guiding aguidewire, device, etc. into one or more of the additional lumens 41a-d.

In aspects, the additional lumens 41 a-d may be accessed by a guidewireand/or system in accordance with the present disclosure as part of sucha procedure. In aspects, the additional lumens 41 a-d may have adiameter of less than 2 mm, less than 1 mm, less than 0.5 mm, or thelike. In aspects, a method may include delivering the tip of a guidewirein accordance with the present disclosure into one or more of the lumens37 a,b, 39 a-d, 41 a-d and assessing physiologic activity associatedtherewith, treating the nerves within the vicinity of the lumen(s) 37a,b, 39 a-d, 41 a-d, and assessing the extent of the treatment.

Such aspects may be applied to the treatment of one or more alternativedisease states, or organs within the body. In aspects, a method, system,or guidewire, in accordance with the present disclosure may be used toassess the completion, response to, predict the response to, diagnose adisease state, etc. associated with neural traffic or neuroendocrinefunctions associated therewith in accordance with the presentdisclosure.

FIG. 2p illustrates aspects of a guidewire 2250 in accordance with thepresent disclosure placed within a lumen 25. The guidewire 2250 mayinclude one or more zones 2254, 2252 in accordance with the presentdisclosure. The guidewire 2250 includes a sensing zone 2254 locatedalong the length thereof for interfacing with the lumen wall proximallyto a treatment site. The guidewire 2250 includes a sensing tip 2252located at the distal tip thereof for interfacing with the lumendistally to a treatment site. The guidewire 2250 includes one or moremicroneedles 2256, which may be advanced from the body of the guidewire2250 into the wall of the lumen 25 into which it has been placed as partof a procedure. Such needle advancement or retraction 2258 may becoordinated by an operator, a controller 2262, etc. In aspects, themicroneedles 2256 may provide a means for delivering a chemical agent2260 into the tissues surrounding the lumen 25. In aspects, themicroneedles 2256 may include one or more electrodes to monitor and/orinterface (e.g. stimulate, ablate, etc.) the local tissues upondeployment therein. In aspects, the guidewire 2250 may be configured soas to deliver the microneedles 2256 into the adventitia of the lumen 25,or optionally directly into the parenchyma of an organ to be treated.Such a configuration may be advantageous to provide a neurotoxin, acancer treating agent, a neuroblocking agent, a neurostimulating agent,etc. into the target tissues as part of a treatment procedure inaccordance with the present disclosure.

FIGS. 3a-d show aspects of a sensing guidewire in accordance with thepresent disclosure coupled with a second surgical tool or system formonitoring locations in a body before, during and/or after a procedure(e.g. surgical procedure, diagnostic procedure, signal assessment,etc.). FIG. 3a shows a sensing guidewire 301 with a sensing tip 303 eachin accordance with the present disclosure. The sensing guidewire 301 isshown placed within the parenchyma of an organ 1 (in this case, akidney), having been routed to the organ 1 via a lumen 5 (e.g. forpurposes of discussion a renal artery 5, a vein 7, a ureter 9, etc.).The guidewire 301 may provide a path for the delivery of a secondsurgical tool, in this case a balloon catheter 309. The balloon catheter309 may include a balloon with one or more energy delivery elements,electrodes 311 or the like, configured so as to provide stimulationand/or ablation to one or more anatomical sites adjacent to the lumen 5.Such stimulation and/or ablation processes performed by the catheter 309may be coupled with one or more recording events (or stimulation events)performed with the guidewire 301.

In aspects, the balloon catheter 309 may be inserted into the bodyfollowing the guidewire 301 until the balloon is placed within the lumen5. The balloon may be inflated so as to bias one or more energydelivering elements 311 towards the wall of the lumen 5 as part of atreatment, a monitoring session, a stress test, etc.

In aspects, a balloon equipped with one or more electrodes 311 may beconfigured to deliver a stimulating and/or ablating current into theadjacent anatomy between one or more of the electrodes on the balloonand a remote electrode patch (not explicitly shown), so as to form asubstantially radial current 313, or between two or more electrodes onthe balloon to form substantially circumferential current 315, orlongitudinal current 317. In aspects, physiologic response to thecurrent 313, 315, 317 may be monitored by the guidewire 301. In aspects,the guidewire 301 may contribute current to the stimulation and/orablation process. In aspects, the balloon may be used to ablate thesurrounding anatomical sites and then to stimulate/sense with one ormore of the proximally oriented electrodes, in conjunction with asensing/stimulating event at the sensing tip of the guidewire 301. Suchinformation may be used to determine the effectiveness of the ablationprocedure, the functionality of the neurological structures between theguidewire 301 sensing tip 303 and the balloon electrodes 311, etc.

The guidewire 301 and/or the balloon catheter 309 may be coupled with asingle controller 305, separate controllers, connectors, etc. so as toperform the intended tasks within the body.

The guidewire 301 may be configured such that the sensing tip 303 isplaced along a region of interest 304 along the delivery route (e.g.such as near to the organ 1, within the parenchyma of the organ 1, alonga vessel 5, 7, 9 coupled to the organ 1, etc.). In aspects, analternative delivery route 312 is shown providing access to the renalpelvis for monitoring, ablation, etc. as part of a procedure inaccordance with the present disclosure.

FIG. 3b illustrates a sensing guidewire 321 in accordance with thepresent disclosure having been advanced along a lumen 5 within a body toan anatomical site of interest 325 (in this case within the parenchymaof an organ 1). The guidewire 321 includes a sensing tip 323 inaccordance with the present disclosure for acquiring one or morephysiologic signals from the anatomical site of interest 325 during aprocedure (e.g. surgical procedure, diagnostic procedure, signalassessment, etc.). The guidewire 321 may be placed along the path insite 325 as shown in order to capture signals relevant to the intendedprocedure. The guidewire 321 may be used to guide anablation/stimulation tool 327 into the lumen 5 so as to properlyposition it to perform one or more stimulation and/or ablation eventsalong the lumen 5 in accordance with the present disclosure. In aspects,the guidewire may include a stylet core, a stiffened element, etc. overwhich the second tool 327 may be advanced during placement. Retractionof the stylet may be used to alter the local stiffness of the guidewire321 thus allowing the second tool 327 to take on a deployed shape (inthis case a helical shape). Thus the second tool 327 may be deployed soas to interface one or more electrodes 329, needle delivery ports,included thereupon etc. with the tissues of the lumen wall 5 and thesurrounding anatomy. As with the other coupled devices in accordancewith the present disclosure, operation of the guidewire 321 and thesecond tool 327 may be coordinated so as to elucidate function of thelocal anatomy, the state of a surgical procedure, completion of asurgical procedure, diagnosis of a functional response to a stress test,etc.

The guidewire 321 and/or the second tool 327 may be coupled with asingle controller 331, separate controllers, etc. so as to perform theintended tasks within the body. In aspects, the second tool 327 may beconfigured to deliver energy and/or a chemical substance to the adjacenttissues. Such energy delivery may be considered between elements on thesecond tool 327 or to a remotely coupled element, so as to apply energyradially 326 to, circumferentially 328 around, axially 322 along, thetarget region, lumen 5, etc. as part of a procedure (e.g. a stimulationprocedure, stress test, surgical procedure, etc.).

The guidewire 321 may be configured such that the sensing tip 323 isplaced along a region of interest 325 along the delivery route (such asnear to the organ 1, within the parenchyma of the organ 1, along avessel 5, 7, 9 coupled to the organ 1, etc.). In aspects, an alternativedelivery route 324 is shown providing access to the renal pelvis formonitoring, ablation, etc. as part of a procedure in accordance with thepresent disclosure.

FIG. 3c shows a sensing guidewire 341 in accordance with the presentdisclosure having been advanced along a lumen 5 within a body to ananatomical site of interest 344 (in this case within the parenchyma ofan organ 1). The guidewire 341 may include one or more sensing tips 343in accordance with the present disclosure for acquiring one or morephysiologic signals from the anatomical site of interest 344 during aprocedure (e.g. surgical procedure, diagnostic procedure, signalassessment, etc.). The guidewire 341 has been positioned within the bodyof a subject and a needle catheter 345 has been directed along theguidewire 341 to a surgical site within the lumen 5. The needle catheter345 may include one or more delivery needles 347, which may be deployedso as to interface with the anatomy in the vicinity of the lumen wall 5.In aspects, the delivery needles 347 may be hollow so as to administer asubstance 350 (e.g. a fluid, a solid powder, or gel, a medicament, etc.)to the anatomy in and around the lumen wall 5. Such medicament 350 maybe configured to alter functionality of the tissues in the vicinity ofthe lumen wall 5, to chemically ablate one or more neurologicalstructures, etc. As with the other coupled devices in accordance withthe present disclosure, operation of the guidewire 341 and the needlecatheter 345 may be coordinated so as to elucidate function of the localanatomy, the state of a surgical procedure, extent of an ablationprocess, etc.

In aspects, the guidewire 341 may be left in place and the needlecatheter 345 removed after delivery of the bolus of substance 350 to thewalls of the lumen 5. After removal of the needle catheter 345, theguidewire 341 may be used to monitor for a prolonged period of time inorder to identify if the substance 350 was properly delivered to theintended tissues (i.e. to determine if the neurological function returnsafter the intervention, or if the change in function has been relativelypermanent in scope).

In aspects, the needle catheter 345 may include features 351 so as tolimit the depth with which the delivery needles 347 may enter into thelumen wall 5 during deployment, as well as to gauge the depth at which amedicament 350 is delivered into the tissues. In aspects, the needlecatheter 345 may include a plurality of delivery needles 347 so as toboth stabilize the catheter 345 as well as to deliver medicament 350 toa plurality of locations within the adjacent tissues.

In aspects, the delivery needles 347 may include one or more electrodes349 configured for stimulation, ablation, and/or sensing with eachfunction being suitable for coordinating with the guidewire 341 duringan interventional procedure.

The guidewire 341 and/or the needle catheter 345 may be coupled with asingle controller 353, separate controllers, connectors, etc. so as toperform the intended tasks within the body.

The guidewire 341 may be configured such that the sensing tip 343 isplaced along a region of interest 344 along the delivery route (such asnear to the organ 1, within the parenchyma of the organ 1, along avessel 5, 7, 9 coupled to the organ 1, etc.). In aspects, an alternativedelivery route 342 is shown providing access to the renal pelvis formonitoring, ablation, etc. as part of a procedure in accordance with thepresent disclosure.

FIG. 3d shows a sensing guidewire 361 in accordance with the presentdisclosure having been advanced along a lumen 5 within a body to ananatomical site of interest 364 (in this case within the parenchyma ofan organ 1). The guidewire 361 may include one or more sensing tips 363in accordance with the present disclosure for acquiring one or morephysiologic signals from the anatomical site of interest 364 during aprocedure (e.g. surgical procedure, diagnostic procedure, signalassessment, etc.). The guidewire 361 has been positioned within the bodyof a subject and an ultrasound catheter 365 has been directed along theguidewire 361 to a surgical site within the lumen 5.

The ultrasound catheter 361, may include a balloon (as shown) or anenergy directing element, configured so as to delivery and/or direct thedelivery of ultrasonic energy 367 to one or more tissue sitessurrounding the lumen 5 during a surgical procedure. In aspects, suchultrasonic energy 367 may be used to disrupt the regular neurologicaltraffic there along, and/or to ablate the neurological anatomy locatedin the vicinity of the lumen 5.

In aspects, the ultrasound catheter 365 may include one or moreelectrodes configured for stimulation, ablation, and/or sensing witheach function being suitable for coordinating with the guidewire 361during an interventional procedure.

The guidewire 361 and/or the ultrasound catheter 365 may be coupled witha single controller 370, separate controllers, connectors, etc. so as toperform the intended tasks within the body.

As with the other coupled devices in accordance with the presentdisclosure, operation of the guidewire 361 and the ultrasound catheter365 may be coordinated so as to elucidate function of the local anatomy,the state of a surgical procedure, extent of an ablation process, etc.

The guidewire 361 may be configured such that the sensing tip 363 isplaced along a region of interest 364 along the delivery route (such asnear to the organ 1, within the parenchyma of the organ 1, along avessel 5, 7, 9 coupled to the organ 1, etc.). In aspects, an alternativedelivery route 362 is shown providing access to the renal pelvis formonitoring, ablation, etc. as part of a procedure in accordance with thepresent disclosure.

FIGS. 4a-c show devices 400, 420, 440 in accordance with the presentdisclosure placed so as to monitor activity within an organ 1 within abody. FIG. 4a illustrates aspects of a monitoring device 400 including asensing guidewire 401 with a sensing tip 403 each in accordance with thepresent disclosure. The sensing guidewire 401 may be configured anddimensioned for percutaneous placement (i.e. through the skin 11 of thesubject) of the sensing tip 403 thereof into an organ 1 (i.e. in thiscase into the renal cortex 3 of the kidney 1) for monitoring one or morephysiologic signals therefrom during a procedure (e.g. a monitoringprocedure, a surgical procedure, etc.). In aspects, the guidewire 401may be delivered through a cannula 405 (e.g. a polymer cannula, a hollowneedle, etc.). In aspects, the cannula 405 may be inserted through theskin 11 using procedures similar to those used to place an intravenouscannula, an infusion set, or the like. In aspects, the placementprocedure may be guided by an imaging system, an ultrasound probe, etc.

In aspects, the guidewire 401 may be coupled to an interconnectionmodule 407 (e.g. a module including interconnects, and/ormicrocircuitry), thus providing electrical and/or optical communicationbetween one or more sensors and/or electrodes in the sensing tip 403with a controller 409 each in accordance with the present disclosure.

In aspects, one or more elements of the sensing tip 403 may bedeployable once inserted within the organ 1. Such deployable aspects(e.g. deployable tines, microfingers, etc.) may be advantageous formaintaining the position of the sensing tip 403 within the organ 1during use. In aspects, the sensing tip 403 may include a plurality ofsensors or electrodes for capturing physiologic information from theorgan 1 during the monitoring procedure.

FIG. 4b shows a device 420 for prolonged monitoring of physiologicparameters from an organ 1 in a body. The device 420 may be deliveredpercutaneously with the help of a delivery needle, biopsy needle, via acannula, etc. The device 420 may include a sensing guidewire 421 with asensing tip 423 each in accordance with the present disclosure. Inaspects, the sensing guidewire 421 may be sufficiently flexible and/orstretchable so as to provide minimal stress at the anatomical site ofinterest during the monitoring period. In aspects, the sensing tip 423may include one or more electrodes, microfingers, and/or sensors inaccordance with the present disclosure. In aspects, one or more of themicrofingers or electrodes may be hooked, anchored, and/or include oneor more retaining aspects so as to maintain the position of the sensingtip 423 within the organ 1 during the monitoring period.

As shown in FIG. 4b , the guidewire 421 may be interconnected with asignal recording module 425. The signal recording module 425 is shownattached to the skin 11 with an adhesive 427. The signal recordingmodule 425 may include one or more microcircuits configured to interfacewith the sensing tip 403 and generate one or more signals therefrom,suitable for transfer to an external unit (e.g. an interconnectedcontroller, a wirelessly connected device, a network, a LAN, a WAN, amemory module for storage and later recall, etc.). In aspects the signalrecording module 425 may be configured to translate the capturedphysiologic signals into a wireless signal 429 to communicate with aphone, a surgical control system, a hospital network, etc.

In aspects, one or more of the deployable and or retaining aspects ofthe sensing tip 423 may be reversible and/or biodegradable, such thatthe device 420 may be easily removed from the body after the monitoringperiod has been completed.

FIG. 4c illustrates aspects of a device 440 including an implantablemodule 441 and a signal recording module 445. The implantable module 441may include one or more sensors and/or electrodes 443 each in accordancewith the present disclosure. The implantable module 441 may include oneor more microcircuits configured to accept power from an incoming energysource 451 or to harvest power from the surroundings (e.g. via kinetic,thermal gradient, pH gradient, enzymatic fuel cell, etc.) so as to powera preamplifier circuitry and to relay a wireless signal 449 back to thesignal recording module 445, the wireless signal 449 relating to one ormore physiologic aspects of the anatomical site of interest (e.g. withinthe organ 1, or within the body). In aspects, the energy source 451 maybe transmitted by the signal recording module 445 in to the body for usein the monitoring process. In aspects, the signal recording module 445may be secured to the skin 11 of the body with an adhesive interface447.

In aspects, the implantable module 441 may be placed with a needle, abiopsy needle, via a cannula, optionally inserted through the skin 11with ultrasound guidance, etc. In aspects, a plurality of implantablemodules 441 may be placed at various sites within the body (e.g. withinan organ 1, along a lumen wall 5, etc.) so as to capture spatiallydependent information from the subject during the monitoring session.

In aspects, one or more of the devices 400, 420, 440 in accordance withthe present disclosure may be used to monitor one or more physiologicparameters during a stress test in accordance with the presentdisclosure.

In aspects, the implantable module 441 may include one or more sensingtips in accordance with the present disclosure and a tether. The tethermay include a fibrous cord to mechanically connect the interfacingportion to a location on the body (such as an entry port, a site on theskin 11, etc.). The tether may include means for electricallycommunicating between an externally placed device and the interfacingportion and/or sensing tips included therein. The tether may include alubricous coating to substantially limit bonding between the tether andadjacent tissues during the placement period. The interfacing portionmay be equipped to monitor one or more physiologic parameters of theadjacent anatomical structure for a prolonged period followingplacement.

The signal recording module 445 may include one or more microcircuitsconfigured to interface with implanted module 441 and generate one ormore signals therefrom, suitable for transfer to an external unit (e.g.an interconnected controller, a wirelessly connected device, a network,a LAN, a WAN, a memory module for storage and later recall, etc.). Inaspects the signal recording module 445 may be configured to translatethe captured physiologic signals into a wireless signal 452 tocommunicate with a phone, a surgical control system, a hospital network,etc.

FIGS. 5a-d illustrate aspects of a fiber based sensing guidewire 501 inaccordance with the present disclosure. The guidewire 501 may includeone or more fibers 503, arranged so as to form an array. In aspects, thefibers 503 may be semiconducting or conducting structures, suitable forelectrically communicating between the tips thereof and a moreproximally placed microcircuit, or connector suitable for coupling thefiber tips 507 to a controller 509 in accordance with the presentdisclosure. In aspects, the fibers 503 may be packed into a jacket 505.The jacket 505 may be biased towards the fibers 503 so as to provide thedesired packing, but yet provide for longitudinal movement between thefibers 503 and the jacket 505 so as to allow for deployment of thefibers 503 as well as for maintaining a highly flexible guidewire 501.In aspects, one or more segments of the fibers 503 may be bondedtogether so as to provide structural rigidity, maintain unified movementof the bundle during deployment, provide tight seals along the jacket505, etc.

In aspects, the jacket 505 may be formed from a microspring, aninsulated microspring, a polymer sheath, an elastomer sheath, a shrinktube, a braided thin walled tube, etc.

In aspects, each fiber 503 may be electrically isolated from the others,so as to provide a series of sites (i.e. at fiber tips 507) in contactwith the local anatomy for sensing one or more physiologic parameters.In aspects, the fibers 503 may be formed sufficiently small such thatsingle through to multi-unit recordings may be made from the localanatomy within the subject.

Such a configuration may be advantageous for accessing very smallanatomical sites of interest within the body but yet provide suitablemapping capability, or improve the prospects of obtaining viable signalsfrom heterogeneously distributed neurological features given a highfiber tip 507 count.

In aspects, each fiber 503 may be held in close proximity to the otherfibers 503 yet be only slidingly coupled thereto (i.e. so as to allowfor movement of adjacent fibers with respect to each other). Such aconfiguration may be advantageous to improve the flexibility of theoverall guidewire 501.

In aspects, such a configuration may provide improved magnetic fieldcompatibility (for use within MRI guided surgical procedures), reduceheating of local tissues under a strong magnetic field, etc.

In aspects, the fibers 503 may be interfaced with an ultrahigh densityinterconnect, suitable for interfacing directly with each element of thebundle.

FIG. 5b shows aspects of a cross section of a fiber 503 in accordancewith the present disclosure. The fiber 503 may include a conducting,resistive and/or semi-conductive core 511 (e.g. platinum, carbon,titanium, stainless steel, nickel titanium, silver, gold, spring steel,etc.). In aspects, the core 511 may be dimensioned with a diameter 515of less than 25 μm, less than 12 μm, less than 7 μm, less than 5 μm,less than 2 μm, etc. In aspects, one or more segments of the core 511may be covered with a clad layer 512. The clad layer 512 may include apassivating material, a highly conducting material, a bioactivematerial, etc. configured so as to isolate the core 511 from thesurroundings, to improve the longitudinal conductivity of the core 511(i.e. in the case of a metallic clad layer 512), provide unique analyteidentification means (i.e. in the case of a bioactive clad layer 512, anenzymatic layer, etc.). In aspects, the clad layer 512 may result in aclad diameter 516 of less than 100 μm, less than 25 μm, less than 12 μm,less than 6 μm, less than 4 μm, etc. In aspects, the clad layer 512 maybe thinner than 1 μm, thinner than 0.5 μm, thinner than 0.1 μm, etc. Inaspects, the clad layer 512 may provide improved optical transmissiondown an optically oriented fiber 503.

In aspects, one or more segments of the clad layer 512 or the core 511may be coated with an insulating layer 513. The insulating layer 513 mayinclude a dielectric material, a thick walled polymer material, aceramic, etc. The insulating layer 513 may be configured to enhanceelectrical isolation and/or reduce cross talk between fibers 503 oversegments of the guidewire 501. In aspects, the insulating layer 513 mayhave a diameter 517 of less than 200 um, less than 100 um, less than 50um, less than 25 um, less than 10 um, etc. In aspects, the insulatinglayer 513 may be provided with differing thickness (i.e. differentoverall fiber diameter 517) along alternative segments thereof. In onenon limiting example, the insulating layer 513 is relatively thin nearto the distal region of the guidewire 501 but increases in thickness inthe proximal direction thereof.

In aspects, the clad layer 512 and/or the insulating layer 513 may beremoved and/or otherwise not present over one or more segments of thefiber 503. Such a configuration may be advantageous for altering theflexibility, altering the intercommunication of the fibers 503, allowfor interconnects between fibers 503, etc. over a particular segment ofthe guidewire 501.

In aspects, the clad layer 512, and/or the insulating layer 513 may beapplied electrochemically to the core 511. In aspects, one or more ofthe layers 512, 513 may be applied via electrodeposition, aself-assembly process, a cataphoretic process, etc. In aspects, such aprocess may be used to form a highly uniform layer 512, 513 on the core511.

FIG. 5c shows aspects of a bundle of fibers 503 in accordance with thepresent disclosure configured near to the wall of the jacket 505 of theguidewire 501 in accordance with the present disclosure. A detailedimage B is shown to highlight the arrangement within the guidewire. Inaspects, such a configuration may provide for a highly flexibleguidewire 501 including hundreds to thousands of fibers 503 forinterfacing with the anatomical site of interest while maintaining anoverall diameter and flexibility that allows for access to small vesselswithin a body (e.g. access into an organ parenchyma, small arteries,veins, large arterioles, large venules, etc.).

In aspects, the packing density of the fibers 503 may be provided so asto more easily interface with the fibers 503 near to the proximal end ofthe guidewire 501.

FIG. 5d shows aspects of a deployment mechanism for a fiber guidewire521. The fiber guidewire 521 may include one or more fibers 523 and/or ajacket 525 each in accordance with the present disclosure. The fibers523 may be configured into a bundle, representing the interior aspectsof the guidewire 521. The jacket 525 may help to insulate and/or shieldthe fibers 523 from the surroundings during placement within a body. Inaspects, the guidewire 521 and fibers 523 may be coupled with aconnector, a microcircuit, a preamplifier, and/or a controller 529 inaccordance with the present disclosure.

In aspects, the fibers 523 or a segment there along may be bondedtogether with temporarily restraining matrix 527 (e.g. a biodegradablematrix, an electrochemically degradable matrix, a water soluble matrix,etc.). Such a configuration may be advantageous for assisting withdeployment 533 of the fibers 523 once the guidewire 521 has been placednear to the anatomical site of interest. Alternatively, additionally, orin combination, the jacket may be dimensioned and configured so as to beretractable for deployment of the fibers after placement (i.e.retractable so as to expose the fibers after delivery to the site ofinterest).

In aspects, the restraining matrix 527 may include a bolus of astressing medicament (e.g. a neurostimulant, a neurodepressant, avasodilator, a vasoconstrictor, a neuroblocking agent, glucose, insulin,etc.). In aspects, the bolus may be delivered into the organ 1 of thesubject while the guidewire 521 monitors the associated physiologicresponse thereto at the site of interest.

FIGS. 6a-e show aspects of flexible multi-electrode guidewire tips 601a,b, 621, 661 in accordance with the present disclosure. FIG. 6a showsmonolithic guidewire tips 601 a,b including one or more tines 603 a,b,each tine including one or more sensors and/or microelectrodes 605 a,beach in accordance with the present disclosure configured forinterfacing with an anatomical site of interest within a body. Theguidewire tip 601 a,b may be at least partially formed from a flexiblesubstrate 607 a,b in accordance with the present disclosure configuredand dimensioned to form tines as well as provide electricalinterconnection of components placed there upon, or integrated into thesubstrate 607 a,b.

In aspects, the substrate 607 a,b may include a flexible polymer,polyimide, PET, PEN, an elastic material, a silicone, an elastomer, anelectroactive polymer, or the like known in the field of flexibleelectronics.

In aspects, the guidewire tip 601 a,b may include one or moremicrocircuits 611 a,b in accordance with the present disclosure. Themicrocircuits 611 a,b may be configured to perform one or more functionssuch as signal routing, multiplexing, demultiplexing, preamplification,signal amplification, filtering processes, differential coupling to areference electrode, signal conditioning function, analog to digitalconversion, communication, power management, combinations thereof, andthe like. The substrate 607 a,b may include one or more conductingtraces 609 a,b placed so as to interconnect the sensors and/orelectrodes 605 a,b with the microcircuits 611 a,b.

In aspects, one or more of the conducting traces 609 a,b may include ametal, a meandering metal trace (i.e. so as to improve the flexibilityor stretch capability thereof), an organic conductor, a printedstructure, a physically deposited structure, or the like.

In aspects, one or more microelectrodes 605 b may be formed at theextreme tip of a tine 603 b. Such formation may be achieved by routingone or more traces 609 b to the tip and severing the tip so as to exposeonly the most distal part of the trace 609 b so as to form theinterconnect for the microelectrode 605 b. The interconnect may beplated with an interfacing material, such as a metal, platinum, acomposite, a conjugated polymer, etc. so as to form the microelectrode605 b and so as to enhance coupling between the microelectrode 605 b anda surrounding anatomical site of interest.

The substrate 607 a,b may include interconnects for coupling with powerand signal lead wires 613 a,b. The microcircuit 611 a,b may beconfigured to communicate with an outside communication module, acontroller, or the like (not explicitly shown). In aspects,communication may be in the form of a bus protocol such as I²C, 1-wire,SPI, serial, etc. In aspects, the lead wires 613 a,b may be configuredand interconnected to power management hardware configured so as toprovide power and signal communication along the same leads. Such aconfiguration may be advantageous to minimize the number of lead wires613 a,b within the guidewire.

After attachment of components (e.g. sensors, microcircuit(s) 611 a,b,lead wires 613 a,b, etc.) the substrate 607 a,b may be rolled 615 toform a completed guidewire tip 617. FIG. 6b shows a completed guidewiretip 617 with an integrated jacket 619 coupled to the tip so as toreinforce the electrical interconnection of the substrate 607 a,b, thelead wires 613 a,b, and/or the microcircuits 611 a,b. In aspects, thejacket 619 may also provide increased electrical isolation between themicrocircuits 611 a,b, the traces 609 a,b, the lead wire 607 a,binterconnects, and the surroundings.

FIG. 6c illustrates a non-limiting example of a guidewire tip 621 withdeployable tines 603. The tines 603 may be deployed from within a jacket623 by retraction 625 of the jacket 623, advancement 627 of the tines603 or a combination thereof. Such action will lead to deployment 629 ofthe tines 603 so as to monitor a physiologic parameter during aprocedure in accordance with the present disclosure.

Two non-limiting examples of deployed configurations are shown in FIG.6c , a configuration where the tips of the tines 603 are free and theset shape of the tines 603 results in a flower like formation upondeployment from the jacket 623. In aspects, the interconnects 631 on thesubstrate 607 may be dimensioned and/or encapsulated so as to form asoft seal against the jacket 623. Such a configuration may beadvantageous to minimize fluid ingress to the guidewire during aprocedure.

In aspects, the lead wires 603 may be coupled with a controller 630 inaccordance with the present disclosure.

Another example of a deployed configuration is shown in FIG. 6c , aconfiguration where the tips of the tines 603 are held together with arestraining tip 635 so as to form a basket shape upon deployment 625.The basket may be retained in a jacket 639 of the device beforedeployment 625. In aspects, the restraining tip 635 may include anadditional pull wire 632 configured such that relative movement of thepull wire may provide the forces necessary to deploy 625 the tines 603(i.e. to convert the tines 603 from a collapsed shape to a basket-likeshape).

In aspects, one or more of the tines 603 may be coupled with amicrocircuit 637 in accordance with the present disclosure. Themicrocircuit 637 may be embedded into the device substantially near tothe tines 603, within 400 mm thereof, 100 mm thereof, within 20 mmthereof, within 5 mm thereof, etc.

FIG. 6d illustrates a close up view of a tine 603 in accordance with thepresent disclosure. The tine 603 includes a plurality of electrodes 605arranged along the tine 603 with a predetermined spacing 642. The tine603 is constructed with a predetermined width 641, which may be taperedand/or otherwise shaped along the length of the tine 603. The tine 603may include one or more traces 609 to interconnect the electrodes 605with one or more microcircuits. The tine 603 may be generallyconstructed from a substrate 607 in accordance with the presentdisclosure. In aspects, the substrate 607 may be constructed from alaminate composite structure, including a base substrate, the traces,overcoats, etc. In aspects, the electrodes 605 may be configured so asto extend beyond the height of the substrate 607 such as by forming theelectrodes 605 as bumps, generating whisker like features on theelectrodes 605, plating the electrodes 605, etc.

FIG. 6e shows aspects of a guidewire tip 661 in an unraveled and awrapped configuration. In the unraveled configuration the guidewire tip661 may include one or more tines 651 formed from a substrate 652 shapedso as to form a tine envelope 655. One or more components on the tinesinterconnected with one or more chipset(s) 653 located at the root ofthe substrate 652. In aspects, the rolling process 657 may be used toarrange the tines 651 into a completed guidewire tip 661. Based upon theshape of the tine envelope 655, the tips and/or electrodes associatedwith the tines 651 may be positioned so as to interface with an elongatespan of a lumen into which the guidewire tip 661 is placed. In aspects,the guidewire tip 661 may be formed into a guidewire with the additionof a jacket and/or a coil 663, etc.

FIGS. 7a-b show aspects of a guidewire 701 and surgical device 705 eachin accordance with the present disclosure, positioned within an organ 1within a body. FIG. 7a shows a guidewire 701 in accordance with thepresent disclosure. The guidewire 701 includes a sensing tip 703 inaccordance with the present disclosure. The guidewire 701 is shownpositioned such that the sensing tip 703 is coupled with an anatomicalsite of interest 13 (i.e. one or more sites along the renal pelvic wall,etc.). In aspects, the guidewire 701 may be configured to monitorafferent nerve traffic associated with the receptors lining the renalpelvic wall 13. An additional surgical device 705 is shown having beendelivered to the organ 1 via the guidewire 701.

In FIG. 7a the surgical device 705 is a fluid exchange catheter,configured with a plurality of lumens so as to deliver fluid 709 andreturn fluid 711 to an external unit (not explicitly shown). Theexternal unit may include a heating element so as to provide a warmfluid to be circulated through the surgical device 705 to the intendedsurgical site (in this non-limiting example, the renal pelvic wall). Inaspects, the fluid delivery may be used to increase the temperature ofthe wall of the renal pelvis to more than 40° C., more than 50° C., morethan 60° C. or the like. Such an operation may be advantageous forblunting the activity of the afferent nerves within the wall of therenal pelvis. In aspects, alternative surgical tools, ablationtechniques, etc. may be implemented as part of the surgical procedure(i.e. an RF or microwave ablation instead of a hot fluid lavage). Inaspects, the fluid delivery catheter may be configured to deliver abolus of a neuroblocker, a neurostimulant, a neurodepressant, etc. Inaspects, the fluid delivery catheter may be configured so as to providea portion of a stress test for the organ 1 in accordance with thepresent disclosure.

In aspects, the surgical device 705 may include a balloon 707 tofacilitate positioning, block off other regions of the body from asaline lavage, facilitate intimate contact with a lumen during asurgical procedure, combinations thereof, or the like.

In aspects, the guidewire 701 and/or surgical device 705 may be coupledwith a controller 713, microcircuit, preamplifier, connector, or thelike each in accordance with the present disclosure.

FIG. 7b illustrates aspects of a method for modulating afferent nervetraffic in accordance with the present disclosure. The method includesmonitoring the afferent nerve activity, treating the afferent nervesand/or receptors, and evaluating the afferent nerve activity posttreatment to determine if the traffic has been modulated. In aspects,the evaluation may be performed by comparing a nerve activity metricbefore and after treatment (e.g. a change in integrated activity level,a change in phasic response, a change in action potential firing rate, achange in the spectral content of the firing, etc.). In aspects, themethod may include varying the pressure applied to the afferent nervesand/or receptors and monitoring afferent nerve activity during suchchanges.

Additionally, alternatively, or in combination with the monitoring ofelectrophysiological activity, the method may include monitoring one ormore physiologic parameters in accordance with the present disclosureand assessing changes in the parameters before, during, or for a periodof time following application of a procedure to the target tissues.

One or more of the steps may be completed with a guidewire or surgicaltool in accordance with the present disclosure.

FIGS. 8a-c show aspects of a device in accordance with the presentdisclosure configured and dimensioned to interface with neural body(i.e. as shown in this non-limiting example, a carotid body 15). FIG. 8ashows a method for modulating functionality of, neural activity from,afferent activity from, or the like of a carotid body 15 of a subject,the method includes accessing the carotid body 15 and optionallymonitoring activity at one or more sites 811 within or in the vicinityof the carotid body 15. In aspects, the method may include accessingregions near the surface of the carotid body 15, deep within the carotidbody 15, etc. In aspects, the method may include selectively stimulatingand/or stressing one or more regions of the carotid body 15 andmonitoring the physiologic response at the sites 811 and/or systemicallyto the stimulus/stress. In aspects, the stimulus/stress response may beused to identify regions of the carotid body 15 that are suitable forneuromodulation to treat a particular condition. In aspects, the methodmay include selectively treating one or more sites 811 within or in thevicinity of the carotid body 15. In aspects, the method may includemonitoring activity and/or local physiologic response to the treatmentat one or more of the sites 811 to determine the extent of theprocedure, to evaluate when the procedure has been completed, to decidewhether or not to continue with the procedure, etc. The method mayinclude ablating a portion of the carotid body 15, or a neurologicalstructure coupled thereto, in accordance with the present disclosure. Inaspects, the method may include using a guidewire and/or surgical devicein accordance with the present disclosure to perform one or more of theabove steps.

In aspects the method may include dragging one or more electrode arraysin accordance with the present disclosure along a lumen in the vicinityof the carotid body 15 in order to locate the body, locate neurologicalfeatures of interest associated with the body, locate one or morebaroreceptors, map activity thereof, map functional changes thereof dueto application of a treatment or stress thereto, evaluate the functionthereof, and/or treat one or more such structures.

FIG. 8b shows aspects of a surgical device 801 in accordance with thepresent disclosure. The surgical device 801 may be delivered to thecarotid bifurication 19 within a subject through the common carotidartery 17 and positioned within the carotid bifurication 19, or alongeither of the external carotid artery 21 or the internal carotid artery23 so as to access the carotid body 15 with one or more componentsthereof. The surgical device 801 may be configured so as to deploy oneor more sensors and/or electrodes each in accordance with the presentdisclosure onto the wall of the artery 17, 21, 23 or through the wall ofthe artery 17, 21, 23 into the carotid body 15 or the tissues in thevicinity thereof. In aspects, the surgical device 801 may include one ormore microneedle electrodes, fluid delivery needles, etc. each inaccordance with the present disclosure so as to penetrate through thewall of the artery 17, 21, 23 and gain access to the carotid body 15.One or more elements within the surgical device 801 may be coupled witha connector and/or controller 802 at the proximal end thereof. Thesurgical device 801 may include a landing region 810 configured so as toretain a position along a wall of an adjacent lumen 17, 21, 23 duringdeployment, monitoring, etc.

During use of a surgical device 801 in a method in accordance with thepresent disclosure, the deployed tips 804 may be dragged 806 along thewalls of the lumen 17, 21, 23 so as to map, locate, monitor, stress,stimulate, and/or treat one or more target tissues within the vicinitythereof.

FIG. 8c illustrates aspects of a surgical device 801 interfaced with thecarotid body 15. The surgical device 801 includes a plurality ofneedle-like microfingers 804 in accordance with the present disclosure,each microfinger 804 may be tipped with a sensor and/or electrode eachin accordance with the present disclosure. The microfingers 804 may beadvanced 809 into the tissues around the carotid bifurcation so as tocouple one or more of the sensors and/or electrodes with the carotidbody 15 thus creating one or more monitoring sites 811 a-e within oraround the carotid body 15. The device 801 may include a jacket 807 toalter the stiffness of one or more segments of the device 801, toprotect the microfingers 804 of the sensing tip, etc. In aspects, thedevice 801 may include one or more stabilizing members 805 or balloon,configured so as to stabilize and/or orient one or more regions ofdevice 801 near to the intended surgical site. Once stabilized, themicrofingers 804 may be advanced towards the carotid body 15. Inaspects, the device 801 may include one or more radiopaque markers, ormay be constructed with one or more radiopaque materials in order toassist a surgeon with visualization of the surgical site during theprocedure. In aspects, the stabilizing members 805 may be configured tolimit relative motion between the microfinger tips (i.e. the electrodes)and the carotid body 15 during one or more surgical procedures performedthereon.

In aspects, the surgical device 801 may be used to monitor sites 811 a-ewithin and around the carotid body 15 to assist in selectively ablatingonly a region of the carotid body (e.g. an outer layer, a surface,etc.). In aspects, the surgical device 801 may be used to both sense andselectively ablate regions of the carotid body 15. In such procedures,the sensing may be performed with or without stimulation/stress todetermine the ideal locations within the carotid body 15 to performneuromodulation. Upon determining the ideal locations, an RF current, amicrobolus of neurotoxin, etc. may be injected into key sites amongstthe monitoring sites 811 a-e. Such a procedure may be advantageous forneuromodulating the carotid body 15 while limiting damage to surroundingstructures, or to regions of the carotid body 15 that are to be sparedin the procedure.

As shown in FIG. 8c , the neural body 15 (such as, in this non-limitingexample, a carotid body) may be located in the vicinity of a maincarotid artery 17, an internal carotid artery 21, or an external carotidartery 23. The surgical tool 801 may be configured for placement in alumen 17, 21, 23 in the vicinity of the neural body 15 (i.e. in thiscase a carotid body), neurons coupled thereto 58 a,b, and/or receptors26 (i.e. in this case baroreceptors lining wall 25 of the internalcarotid artery 21). In aspects, one or more elements of the tool 801 maybe configured so as to be actuate-ably advanced 809 into the wall of thelumen 17, 21, 23, or into contact therewith so as to be advanced towardsa target tissue 811 a-e (e.g. one or more regions of the neural body 811a, a region adjacent to the neural body 811 d, nerves and/or nerveplexuses coupled to the neural body 811 b,c, and/or regions includingreceptors 811 e in the vicinity of the neural body 15 and/or the walls25 of the adjacent lumens 17, 21, 23, etc.

In aspects, one or more of the sensing tips 804 may be configured tostimulate, and/or treat one or more regions of the carotid body 15,and/or one or more target tissues 811 a-e as part of a surgicalprocedure. The region of treatment as well as the extent of treatmentmay be monitored and/or controlled by a circuit coupled with one or moreelectrodes on one or more of the sensing tips 804.

In aspects, a probe or array of tips 804 in accordance with the presentdisclosure, including a plurality of electrodes may be configured toexpandingly and/or sequentially treat regions 811 d of the neural body15, and/or surrounding target tissues 811 a-e. In such a configuration,the treatment zone may be extended, starting from a first location asdetermined by the position of a first electrode and/or electrode pair,and may be simultaneously monitored by one or more surroundingelectrodes on one or more of the tips 804, and/or an additional probe(not explicitly shown, alternatively placed within or near to the neuralbody 15, coupled to a neural structure attached to the neural body 15,etc.). As the neural activity changes in the vicinity of one or more ofthe alternative electrodes (as determined by simultaneous and/orsequential monitoring therefrom), the extent of an affected region asformed during the treatment may be tracked and the treatment may behalted at the appropriate time based upon the desired surgical extent ofthe process. In aspects, one or more of the electrodes may beincorporated into the treatment of the target tissues.

In aspects, one or more electrodes and/or sensing tips 804 may beconfigured to monitor, to stimulate, and/or to alter (e.g. deaden orblock neural traffic, ablate the nerves, etc.), neurological activity inone or more nerve bundles 811 a,b extending from the neural body 15.Changes in neural traffic after a surgical procedure, in response to astimulus, or the like may be used to assist in controllably treating oneor more regions of target tissue 811 d in the neural body 15, or othertarget tissues 811 a-e in the vicinity thereof.

FIG. 9 shows aspects of a multi-tool based approach to monitoring and/orsurgically interacting with a neural body (e.g. a carotid body 15), inaccordance with the present disclosure. FIG. 9 shows a plurality ofsurgical tools 921, 941 after having been delivered to the carotidbifurcation via the common carotid artery 17 and positioned in theexternal and internal carotid arteries respectively. The surgical tools921, 941 include stabilizing anchors 927, 947 which may be deployedfirst in order to orient the tools 921, 941 near to the carotid body 15.Once stabilized, one or more microfingers 923, 943 in accordance withthe present disclosure may be advanced from the devices 921, 941 andonto/through the wall of the carotid bifurcation towards the carotidbody 15. In aspects, one or more of the microfingers 927, 947 mayinclude a sensor and/or electrode 925, 945 configured so as to interfacewith one or more monitoring sites 930, 950 within or in the vicinity ofthe carotid body 15. The surgical tools 921, 941 may be coupled with oneor more controllers 931, 951 in accordance with the present disclosureto capture signals, provide fluids and/or current to one or moremicrofingers 923, 943, etc. as part of the surgical procedure.

In aspects, an RF current may be applied to one or more of theelectrodes 925, 945 in order to treat the carotid body 15. In suchaspects, the current may be passed between one or more of the electrodes925, 945 and a remotely located electrode (not explicitly shown) orbetween 955 two or more of the electrodes 925, 945. Such a method may beadvantageous for selectively controlling the current flow to the regionsof the carotid body 15 in need of treatment. In aspects, the remotelylocated electrode may be a gel electrode placed upon the skin 11 of thebody, a needle electrode, an electrode placed within a nearby vein, orthe like.

FIG. 10 shows aspects of a tool tip for use in a surgical tool inaccordance with the present disclosure. The tool tip includes a jacket1007 including a plurality of ports 1008 through which a plurality ofmicrofingers 1001 and/or anchors 1009 in accordance with the presentdisclosure may pass through in order to couple with a local anatomicalsite of interest, to stabilize the tool tip, etc. The microfingers 1001may include one or more electrodes 1003 and/or sensors at the tipthereof in order to interface with the local anatomical site ofinterest. In aspects, the microfingers 1001 may include an insulatinglayer 1005 configured so as to isolate one or more aspects of themicrofinger 1001 from the surroundings. In aspects, the insulating layer1005 may include a varying thickness, optionally arranged so as to formone or more step transitions along the length of the microfingers 1001.Such steps may be advantageous for limiting the depth of penetration ofthe microfingers 1001 into the local tissues.

In aspects, the microfingers 1001 may include a lumen through which todeliver 1017 a chemical substance, a medicament, etc. to the site ofinterest. Such microfingers 1001 may include one or more electrodes 1003in order to monitor local electrophysiological activity before duringand/or after the procedure.

In aspects, the stabilizing anchors 1009 may be shaped so as to biasagainst a lumen wall, to controllably position the tool tip within alumen, etc. The tool tip may include a balloon for providing similarfunctionality. In aspects, the stabilizing anchors 1009 may be deployedin multiple directions (e.g. towards 1015, away from 1011, a site ofinterest, etc.).

In aspects, the microfingers 1003 and/or anchors 1009 may be slidinglycoupled with the jacket 1007 such that they may be advanced 1013 as partof a deployment procedure. In aspects, the microfingers 1001 may beshaped such that, once stabilized with the anchors 1009, themicrofingers 1001 may be advanced towards 1015 the surgical site ofinterest.

In aspects, the microfingers 1001 and/or stabilizing elements may becoupled with a connector, actuator, and/or a controller 1019 generallysituated at the proximal end of the surgical tool.

FIG. 11 illustrates aspects of coordinated multi-tool procedures beingapplied to an organ 1 as well as highlights placement options forstressing an organ 1 during a procedure in accordance with the presentdisclosure. FIG. 11 demonstrates placement of a sensing guidewire 1101,1103, 1105 into a lumen 5, 7, 9 (e.g. an artery, a vein, a vessel, etc.)within a body so as to access an organ 1 as part of an interventionalprocedure (e.g. a transurethral procedure, a percutaneous procedure,etc.). The guidewire 1101, 1103, 1105 may include a sensing tip inaccordance with the present disclosure. The sensing tip may be deployedas part of a monitoring/stimulating procedure, or the like. In aspects,the guidewire 1101, 1103, 1105 may be used in conjunction with anadditional surgical device 1111, 1113, 1115 so as to couple multi-sitemonitoring and treatment modalities for the organ 1. Although FIG. 11shows the additional surgical device 1111, 1113, 1115 as including aballoon, they may be of any variety of devices suitable for stimulating,stressing, and/or ablating tissues in the vicinity of the associatedlumen 5, 7, 9.

In aspects, a sensing guidewire 1103 may be placed within a first lumen7 (i.e. here shown as a renal vein), while an additional surgical device1113 may be placed in a second lumen 5 (here shown as a renal artery).Coordinated procedures may be carried out with the dual devices in orderto assess functionality of local neurological anatomy, treat localanatomy, determine if treatment has been completed successfully, etc.

In aspects, the additional device 1111, 1113, 1115 may be placed withinthe lumen 5, 7, 9 in order to apply a stress to the organ 1. In aspects,stress may be caused by blocking 1117, 1119, 1121 the lumen 5, 7, 9. Inone non-limiting example, a balloon catheter 1115 placed into the lumen7 in order to establish back pressure on the organ 1 during a monitoringprocedure (e.g. with devices 1101, 1103, and/or 1105 monitoring sites ofinterest related to the organ 1). In aspects, a blocking procedure 1117,1119, 1121 may be used in an artery 5 to relieve pressure on an organ 1,in a vein 7 to increase pressure in an organ 1 (i.e. to simulatevascular overloading) or within a function-related vessel 9 (i.e. aureter) to alter pressure seen by receptors within the organ 1. Suchcombined stress testing and monitoring may be particularly useful inmapping function of the neurologically active tissues coupled to theorgan 1, in selectively treating tissues coupled to the organ 1, etc.

FIG. 12 shows aspects of a method for assessing an anatomical sitewithin a body. The method includes accessing the anatomical site ofinterest within a body (e.g. neuroanatomical features extending to/froman organ, a parenchyma of an organ, a kidney, a liver, a pancreas, aspleen, etc.). The method includes recording one or more physiologicsignals from the site and applying a stress test to the organ. Inaspects the recording may be performed by one or more surgical toolsand/or sensing guidewires in accordance with the present disclosure.

In aspects, the stress test may include releasing a medicament into theorgan (i.e. from the blood supply thereto). Such a step may be performedby one or more sensing guidewires and/or surgical tools in accordancewith the present disclosure.

The recording may be compared against a population norm, a responsebefore/after a surgical procedure, a response between recording sites(i.e. so as to differentiate regions of sympathetic and parasympatheticinnervation), etc.

In aspects, one or more stress tests may be applied to the organ or thesubject in order to better evaluate and/or differentiate functionalityat the monitoring sites.

Some non-limiting examples of stress tests that may be applied in aclinical and/or research setting include a valsalva maneuver, a tilttable test, elevating the legs of a subject, transient sitting tostanding exercises, a change in posture, a movement from a proneposition to a sitting or standing position, a breath hold technique,assessment while awake or asleep, assessment while awake versus underanesthesia, electrostimulation, combinations thereof, and the like. Inaspects, the stress test may include infusion of a vasodilator (e.g.EDHF, potassium, nitric oxide, β-2 adrenergic receptors, histamine,prostacyclin, prostaglandin, vasoactive intestinal peptides, adenosine,ATP, ADP, L-arginine, bradykinin, substance P, niacin, CO2, etc.), or avasoconstrictor (e.g. ATP, muscarinic agents, acetylcholine, NPY,adrenergic agonists, epinephrine, norepinephrine, dopamine, thromboxane,endothelin, angiotensin II, asymmetric dimethylarginine, antidiuretichormone, vasopressin, etc.), a neuroblocker, a neurostimulant, adiuretic, insulin, glucose, beta-adrenergic receptor antagonist,angiotensin-ll converting enzyme inhibitor, calcium channel blocker, anHMG-CoA reductase inhibitor, digoxin, anticoagulants, diuretics, betablockers, ACE inhibitors, one or more steroids (e.g. diflorasone,betamethasone, dexamethasone, clobetasol, prednisolone, mometasone,methylprednisolone, Deprodone, difluprednate, fluocinonide, amcinonide,triamcinolone, difluprednate, hydrocortisone, etc.), testosterone, orthe like, into the body, into the organ, into one or more of themonitoring sites, etc.

In aspects, the stress test may involve the subject performing aphysical activity (such as walking, running, etc.).

In aspects, the stress test may include altering the blood volume of thesubject such as by infusion of a bolus of saline. In aspects, the stresstest may include injecting a quantity of saline in to the body, such as50 cc, 100 cc, 200 cc, more than 400 cc, etc. Such a technique may beadvantageous for evaluating how the organ responds to the stress state,to assist with the diagnosis of a disease state, to evaluate the degreeof stress-response in the local neurological features in the organ, etc.Such monitoring may be advantageous for evaluating the organ responseunder a moderate yet controlled state of stress, so as to evaluate howthe central nervous system adapts to the stress state. In aspects, thepeak activity during stress, the duration of elevated activity after astress test, a comparison between baseline activity versus stressedactivity, etc. may be useful for assisting with a diagnosis or tohighlight abnormal function of a neurological system associated with theorgan. In aspects, the blood volume may be altered by having the subjectdrink a bolus of fluid (e.g. water, electrolytes, etc.) and monitorresponse as the body processes the fluid load.

In aspects, the method may include comparing a result to that of asubject population, a previous test result, aspects within a singlestress test, before and after a procedure, between a resting state andan active state, between an awakened state and a sleeping state, etc.

In aspects, the stress test may include altering the heartbeat of thesubject, such as by pacing the heart out of sync with natural pacingcenters (e.g. so as to lower blood pressure, to cause desynchronizationof the tricuspid valve, etc.), or the like.

In aspects, the stress test may include inserting a balloon catheterinto a lumen that serves the organ and blocking the lumen so as to alterthe blood pressure, nutrient delivery, etc. to the organ whilemonitoring the organ response to such stresses.

In aspects, the stress test may include applying a polarizing potentialto the anatomy in one or more vessels (e.g. so as to temporarily blocktraffic along the neurological features within the vicinity of thevessel, etc.). In aspects, the stress test may include applying atension to the lumen wall.

In aspects, there is provided a system for assessing the localfunctionality of individual nerves in accordance with the presentdisclosure. The system includes a plurality of electrodes configured tointerface with one or more vessels coupled with an organ of interest(e.g. a blood supply, lymph supply, general waste drainage tubes, anartery, a vein, etc.). The electrodes may be arranged so as to captureone or more physiologic signals from sites around the circumference ofthe walls of the lumen before, during, and/or after an organ stresstest, so as to determine the local functionality of the neurologicalanatomy in the vicinity of each electrode. A stress test may include anyof the ones listed above, delivery of a chemical to the organ via theplaced device, etc. During the stress response, particular neurologicalfeatures may exhibit distinct responses to the stress test (e.g.increased activity, decreased activity, changes in spectral response,changes in biorhythm synchronization, etc.), thus distinguishing thelocal function of the neurological features in the vicinity of theelectrodes (i.e. to determine the degree of functionality related to adisease state near to each of the electrodes). Once determined, suchinformation may be used to selectively ablate such tissues, so as toaffect highly differentiated function (e.g. sympathetic orparasympathetic function, neurological features with responsiveness toparticular stimulants, depressants, etc.) thereof. Such selectiveablation may be advantageous for controllably modulating the innervationof the organ, adjusting the balance between contrasting neurologicaltraffic (e.g. reduce traffic of a particular type, etc.).

Such a configuration may be advantageous for mapping and/or tracking anerve structure in accordance with the present disclosure. A surgicaltool in accordance with the present disclosure may be configured tointerface with a nerve plexus. Based on monitoring and/or stimulationand sensing information, the surgical tool may be directed along thelumen wall to better target an overactive nerve. Such a configurationmay be advantageous for tracking an overactive nerve along an organ, avessel, etc. in order to find a more ideal location at which to ablateit. In the non-limiting example shown, a more distal location may beideal for the ablation procedure, as less damage may be caused tosurrounding nerves in the nerve bundle. Other relevant methods arehighlighted throughout the present disclosure and may become apparentthrough reading of the present disclosure.

According to another aspect there is provided methods for performingaspects of a surgical procedure in accordance with the presentdisclosure including monitoring a physiologic signal at a firstmonitoring location (e.g. on an organ, on the wall of a vessel, etc.) togenerate a first signal set, and monitoring a physiologic signal at asecond monitoring location (e.g. on the organ, on the wall of thevessel, elsewhere in the body, etc.) and/or the first monitoringlocation to generate a second signal set. The method includes analyzingthe signal sets to generate a result (e.g. a difference between thesignal sets, a change in a set compared with a previous result, apatient population, etc.). The result may be compared against criteriato determine if a procedure should be performed or not. The proceduremay be a surgical procedure, at least a portion of an ablation,stimulation, further monitoring, etc. The first comparison may be usedto determine if the surgical procedure is having the intended effect onthe tissues. The method may include another comparison to determine ifthe overall procedure is finished or not finished. In the case that theoverall procedure is finished the method may include moving to anothersurgical site, stimulating an alternative tissue site, cleanup and/orremoval of a surgical tool from the body, or the like. In the case thatthe procedure is not finished a procedure may be performed.

In aspects, the method may be performed with a surgical tool inaccordance with the present disclosure.

In aspects, there is provided a method for locating a suitable surgicalsite on a body and performing a surgical procedure thereupon. The methodmay include stimulating a tissue location; monitoring one or morephysiologic parameters at the tissue location or another location in thebody; analyzing the stimulation and/or the monitoring to generate aresult set (e.g. one or more parameters determined from the data setsassociated with either the stimulation, and/or the monitoring, etc.).The method may include assessing the result set to decide if thelocation is suitable for performing a surgical procedure, if it is notthen the system may move and/or assess an alternative location in thebody. If the location is suitable for a surgical procedure then themethod may include performing at least a portion of a surgical procedurethereupon and potentially repeat the overall process. The method mayinclude determining from the result set if the surgical procedure hasbeen completed, if so finalize the procedure, if not perform anotherprocedure and/or move to a new location.

In aspects, the method may include moving to another surgical site,stimulating an alternative tissue site, cleanup and/or removal of asurgical tool from the body, or the like.

In aspects, steps of the method may be performed with a surgical tool inaccordance with the present disclosure.

In aspects, the method may include performing at least part of asurgical procedure (e.g. ablation, chemical delivery, etc.), andmonitoring at a location (e.g. the first location, an alternativelocation, etc.) to determine if the surgical procedure was successful.

Some non-limiting methods for performing a surgical procedure inaccordance with the present disclosure are discussed herein.

In aspects, a method for addressing a surgical site on an organ in abody (e.g. a bowel wall, a stomach, a bladder, a liver, a spleen, akidney, a gland, an artery, a vein, a renal artery, etc.) is considered.The method includes, monitoring one or more local physiologic signals(e.g. an evoked potential, extracellular activity, a neurologicalactivity, MSNA, EMG, MMG, sympathetic tonal change, etc.) in accordancewith the present disclosure at one or more measurement locations alongan outer wall of the organ to determine one or more reference signals;performing at least a portion of a surgical procedure (e.g. an ablation,an excision, a cut, a burn, an RF ablation, an abrasion, a biopsy,delivery of a substance, etc.) in accordance with the present disclosureat or near to one or more surgical locations (e.g. proximal, distal,remotely therefrom, and/or collocated with one or more of themeasurement locations); monitoring one or more local physiologic signalsat one or more of the measurement locations to determine one or moreupdated signals; and comparing one or more reference signals with one ormore updated signals to determine an extent of completion for thesurgical procedure.

In aspects, the extent of completion may include a change, reductionand/or substantial elimination of at least a portion of one or more ofthe local physiologic signals (e.g. reduction in amplitude of afrequency band, reduction in responsiveness, a change in a lag betweenmeasurement locations, a change in cross-talk between measurementlocations, substantial elimination of the signal, etc.).

The step of monitoring to determine an updated signal may be performedbefore, during, and/or after the step of performing at least a portionof the surgical procedure.

In aspects, the step of performing at least a portion of the surgicalprocedure may be repeated. Thus the method may be incrementally applied,so as to head towards completion in a stepwise process without excessiveapplication of the surgical procedure.

In aspects, the method may include waiting after performing at least aportion of the surgical procedure. Monitoring may be performed duringthe waiting procedure, so as to determine a recovery period for thelocal physiologic signal (i.e. a time period over which the localphysiologic signal recovers). Such a recovery period may be anindication of the extent of completion.

In aspects, the method may include stimulating one or more stimulationlocations (proximal, distal, remotely therefrom, and/or collocated withone or more of the measurement locations and/or the surgical locations).The step of stimulating may be coordinated with the step of performingat least a portion of the surgical procedure, and/or with the step ofmonitoring to determine a reference and/or updated signal. Thestimulation may be provided in any form in accordance with the presentdisclosure. In one non-limiting example, the stimulation may include oneor more current pulses, one or more voltage pulses, combinationsthereof, or the like. The step of stimulation may be advantageous forassessing the updated signal at one or more measurement locations and/orbetween two or more measurement locations in the presence of backgroundnoise and/or local physiologic activity.

The method may include monitoring one or more remote physiologicparameters in accordance with the present disclosure at a remotelocation (e.g. an alternative vessel, an organ, a ganglion, a nerve,etc.) substantially removed from the immediate vicinity of the vessel todetermine an updated remote physiologic signal and/or reference remotephysiologic signal.

Some non-limiting examples of remote physiologic parameters that may bemonitored include water concentration, tone, blood oxygen saturation oflocal tissues, evoked potential, stimulation/sensing of nervousactivity, electromyography, temperature, blood pressure, vasodilation,vessel wall stiffness, muscle sympathetic nerve activity (MSNA), centralsympathetic drive (e.g. bursts per minute, bursts per heartbeat, etc.),tissue tone, blood flow (e.g. through an artery, through a renalartery), a blood flow differential signal (e.g. a significantly abnormaland or sudden change in blood flow within a structure of the body, avessel, an organ, etc.), blood perfusion (e.g. to an organ, an eye,etc.), pupil dilation, a blood analyte level (e.g. a hormoneconcentration, norepinephrine, catecholamine, renin, angiotensin II, anion concentration, a water level, an oxygen level, etc.), nerve traffic(e.g. post ganglionic nerve traffic in the peroneal nerve, celiacganglion, superior mesenteric ganglion, aorticorenal ganglion, renalganglion, and/or related nervous system structures), combinationsthereof, and the like.

In aspects, the updated remote physiologic signal and/or referenceremote physiologic signal may be combined and/or compared with one ormore reference signals, and/or one or more updated signals in order todetermine the extent of completion.

In aspects, the method may include selecting a suitable site forperforming a surgical procedure. The step of selection may depend uponone or more monitoring steps, proximity to an alternative surgicallocation (e.g. a previously treated surgical location, etc.).

According to aspects there is provided, a method for treating ananatomical site within a body, including imaging the anatomical site(e.g. with an computed tomography system, HRCT, MRI, fMRI, positronemission tomography, ultrasound, OCT, combinations thereof, or the like)to produce one or more images (e.g. 2D images, 3D images, etc.) thereof,guiding a guidewire, device, and/or aspects of a system in accordancewith the present disclosure to within the vicinity of the anatomicalsite (optionally in combination with the images), and performing aprocedure, and/or treating the anatomical site (e.g. via ablation,chemical delivery, energy delivery, etc.). In aspects, the procedure mayinclude sensing one or more physiologic aspects of the anatomical siteand/or a bodily process related thereto, stimulating the anatomicalsite, etc.

In aspects, a method in accordance with the present disclosure mayinclude advancing a guidewire in accordance with the present disclosureuntil it “bottoms out” against the walls of the lumen including and/orcoupled to the anatomical site.

In aspects, a method in accordance with the present disclosure mayinclude releasing a chemical substance in accordance with the presentdisclosure into, through the wall of, and/or into the adventitia arounda lumen coupled with the anatomical site, and/or associated organ.

In aspects, a method in accordance with the present disclosure mayinclude monitoring one or more physiologic processes with the distal tipof a guidewire in accordance with the present disclosure, before,during, and/or after the release of the chemical substance. The methodmay include assessing the efficacy of a procedure (e.g. ablation,chemical release, chemical ablation, RF ablation, ultrasound ablation,hypothermic ablation, microwave current ablation, radiosurgicalablation, etc.). In aspects, the method may include inducing a temporaryneural block, monitoring the effects of the temporary neural block,and/or creating a substantially long term neural block depending on themonitoring.

In aspects, the steps of monitoring may be completed sequentially.Alternatively, additionally, or in combination, the steps of monitoringmay be effectively continuously applied through the procedure. Thecomparison may be made using one or more data points obtained from oneor more steps of monitoring. The comparison may be made via algorithmiccombination of one or more measurements, a time averaged comparison, aconvolution, or the like.

In aspects, the method may include determining a topographical map fromthe one or more measurements (e.g. from one or more of the signals). Themethod may include determining a topographical map of physiologicfunctionality in the vicinity of the surgical site derived from one ormore of the physiologic signals. The method may include updating thetopographical map after the step of performing at least a portion of thesurgical procedure.

In aspects, the method may include placement of a plurality of surgicaltools, one or more surgical tools (e.g. a procedural tool) placed so asto access one or more of the surgical locations, and one or moresurgical tools (such as a monitoring tool) placed so as to access one ormore of the monitoring locations. In one non-limiting example, aprocedural tool may be placed upon a first organ (e.g. a bowel wall, astomach wall, a kidney, a gland, a renal artery, a left renal artery, arenal vein, a ureter, etc.) and a monitoring tool may be placed upon orwithin a second organ (e.g. an opposing renal artery, a right renalartery, renal vein, a femoral artery, an iliac artery, etc.). Thus, themonitoring tool may be used to monitor one or more of the measurementlocations on the second organ. The procedural tool may be used tosurgically treat one or more surgical locations on the first organ.Additionally, alternatively, or in combination, the procedural tool maymonitor one or more monitoring locations on the first organ, incombination with monitoring performed on the second organ by themonitoring tool, etc.

In aspects, one or more steps of the method may be performed with one ormore surgical tools and or sensing guidewires in accordance with thepresent disclosure.

One or more steps of monitoring may be performed with one or moresensing tips in accordance with the present disclosure.

One or more steps of performing at least a portion of the surgicalprocedure may be performed with one or more sensing tips in accordancewith the present disclosure.

In aspects, a method for RF ablating tissue in accordance with thepresent disclosure may include measuring the local tissue tone before,during, between individual RF pulses, and/or after a train of RF pulses.As the local tissue tone changes during application of the RF pulses,the tonal changes may be used to determine the extent of the therapy. Asthe RF ablation process is applied to the adjacent tissues (via one ormore sensing tips), the tonal measurements (as determined by one or moresensing tips, the same tip through which the RF signal may be applied,etc.) may be monitored to determine an extent of completion of theprocedure. Such an approach may be advantageous as the tonal measurementtechniques may not be significantly affected by the local RF currentsassociated with the RF ablation procedure. The tonal measurements may bemade at monitoring locations sufficiently far from the RF ablation zonethat the local tissues under measurement are not directly affected bythe RF ablation process but may undergo a change in tone as aconsequence of the RF ablation process.

It will be appreciated that additional advantages and modifications willreadily occur to those skilled in the art. Therefore, the disclosurespresented herein and broader aspects thereof are not limited to thespecific details and representative embodiments shown and describedherein. Accordingly, many modifications, equivalents, and improvementsmay be included without departing from the spirit or scope of thegeneral inventive concept as defined by the appended claims and theirequivalents.

What is claimed is:
 1. A guidewire, comprising: an elongate bodydimensioned for insertion into a lumen within a body; and a sensing tipelectrically and mechanically coupled to the elongate body, the sensingtip being configured to interface with the wall of the lumen and toconvey one or more electrophysiological signals associated with anelectrophysiological activity in the vicinity of an anatomical site ofinterest within the vicinity of the lumen; wherein the sensing tipcomprises a plurality of electrodes disposed on a flexible substrate,the flexible substrate being rolled to form the sensing tip.
 2. Theguidewire of claim 1, wherein the sensing tip comprises at least onetine, at least a subset of the plurality of electrodes being arrangedalong the at least one tine with a predetermined spacing.
 3. Theguidewire of claim 1, wherein the sensing tip comprises at least onetine having a width that is tapered along the length of the tine.
 4. Theguidewire of claim 1, wherein the sensing tip comprises at least onetine, at least a subset of the plurality of electrodes being arrangedalong the tine, the at least one tine comprising one or more tracesinterconnecting the subset of the plurality of electrodes with one ormore microcircuits.
 5. The guidewire of claim 1, wherein the flexiblesubstrate comprises a laminate composite structure.
 6. The guidewire ofclaim 1, wherein the laminate composite structure comprises a basesubstrate, one or more traces disposed on the base substrateinterconnecting the plurality of electrodes with one or moremicrocircuits, and one or more overcoats disposed over the one or moretraces and the base substrate.
 7. The guidewire of claim 1, wherein theplurality of electrodes are configured to extend above a height of theflexible substrate.
 8. The guidewire of claim 7, wherein at least asubset of the plurality of electrodes are formed as bumps disposed on asurface of the flexible substrate.
 9. The guidewire of claim 7, whereinat least a subset of the plurality of electrodes comprise whiskerfeatures that extend above the height of the substrate.
 10. Theguidewire of claim 7, wherein at least a subset of the plurality ofelectrodes are plated to extend above the height of the substrate. 11.The guidewire of claim 1, wherein the flexible substrate comprises oneor more tines shape to form a tine envelope.
 12. The guidewire of claim11, wherein at least a subset of the plurality of electrodes aredisposed on the one or more tines of the tine envelope, the subset ofthe plurality of electrodes being interconnected with one or moremicrocircuits located at a root of the tine envelope.
 13. The guidewireof claim 12, wherein the subset of the plurality of electrodes arepositioned on the one or more tines of the tine envelope such that, whenthe tine envelope is rolled, the subset of the plurality of electrodesinterface with different positions of an elongate span of the lumen intowhich the guidewire is placed.
 14. The guidewire of claim 13, furthercomprising at least one of a jacket and a coil disposed surrounding atleast a portion of the rolled tine envelope.
 15. The guidewire of claim1, further comprising one or more stabilizing anchors coupled to theelongate body, the one or more stabilizing anchors being configured todeploy from the elongate body and couple to at least a first lumenproximate the anatomical site of interest.
 16. The guidewire of claim15, wherein the sensing tip is configured to deploy from the elongatebody to interface with a wall of a second lumen.
 17. The guidewire ofclaim 16, wherein the first lumen and the second lumen are the same. 18.The guidewire of claim 16, wherein the sensing tip comprises aninsulating layer configured to isolate one or more portions of thesensing tip from its surroundings.
 19. The guidewire of claim 18,wherein the insulating layer has a varying thickness to form one or morestep transitions along a length of the sensing tip, the one or more steptransitions limiting a depth of penetration of the sensing tip into thewall of the second lumen.
 20. The guidewire of claim 15, wherein the oneor more stabilizing anchors are shaped to bias against a wall of thefirst lumen on deployment from the elongate body.